Π”ΠΈΠΏΠ»ΠΎΠΌ, курсовая, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ Ρ€Π°Π±ΠΎΡ‚Π°
ΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² написании студСнчСских Ρ€Π°Π±ΠΎΡ‚

РасполоТСниС ΠΈ возмоТная Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½Π°Ρ Ρ€ΠΎΠ»ΡŒ участков связывания транскрипционного Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° CTCF Π² локусС 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°

Π”ΠΈΡΡΠ΅Ρ€Ρ‚Π°Ρ†ΠΈΡΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈΠ£Π·Π½Π°Ρ‚ΡŒ ΡΡ‚ΠΎΠΈΠΌΠΎΡΡ‚ΡŒΠΌΠΎΠ΅ΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹

ЦСлью диссСртационной Ρ€Π°Π±ΠΎΡ‚Ρ‹ являСтся идСнтификация сайтов связывания транскрипционного Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° CTCF Π² Π»ΠΎΠΊΡƒΡΠ΅ 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°, Π΄Π»ΠΈΠ½ΠΎΠΉ ΠΎΠΊΠΎΠ»ΠΎ 1 ΠΌΠ»Π½.ΠΏ.Π½., находящСгося ΠΌΠ΅ΠΆΠ΄Ρƒ ΠΌΠ°Ρ€ΠΊΠ΅Ρ€Π°ΠΌΠΈ FXYD5 ΠΈ Π‘ΠΎΡ…7А1. Π­Ρ‚ΠΎΡ‚ локус содСрТит Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ число извСстных Π³Π΅Π½ΠΎΠ² ΠΈ Π΅Π³ΠΎ нуклСотидная ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ ΠΏΠΎΠ»Π½ΠΎΡΡ‚ΡŒΡŽ установлСна, Ρ‡Ρ‚ΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ‚, ΠΊΠ°ΠΊ ΠΊΠ°Ρ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ всС ΠΎΡ‚ΠΎΠ±Ρ€Π°Π½Π½Ρ‹Π΅ элСмСнты с Π±ΠΎΠ»ΡŒΡˆΠΎΠΉ Ρ‚ΠΎΡ‡Π½ΠΎΡΡ‚ΡŒΡŽ, Ρ‚Π°ΠΊ… Π§ΠΈΡ‚Π°Ρ‚ΡŒ Π΅Ρ‰Ρ‘ >

Π‘ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠ΅

  • Бписок сокращСний
  • 1. Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅
  • 2. ΠžΠ±Π·ΠΎΡ€ Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹
    • 2. 1. ВранскрипционныС Ρ„Π°ΠΊΡ‚ΠΎΡ€Ρ‹, содСрТащиС Π΄ΠΎΠΌΠ΅Π½ Ρ†ΠΈΠ½ΠΊΠΎΠ²Ρ‹Ρ… ΠΏΠ°Π»ΡŒΡ†Π΅Π²
    • 2. 2. CTCF — ΠΏΡ€Π΅Π΄ΡΡ‚Π°Π²ΠΈΡ‚Π΅Π»ΡŒ ΠΌΠ½ΠΎΠ³ΠΎΡ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½Ρ‹Ρ… Π±Π΅Π»ΠΊΠΎΠ², содСрТащих ΠΌΠΎΡ‚ΠΈΠ²Ρ‹ Ρ†ΠΈΠ½ΠΊΠΎΠ²Ρ‹Ρ… ΠΏΠ°Π»ΡŒΡ†Π΅Π²
    • 2. 3. Π‘Ρ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Π½Ρ‹Π΅ особСнности
    • 2. 4. ΠŸΠΎΠ»ΠΈΡ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ Π±Π΅Π»ΠΊΠ° CTCF ΠΈ Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΡ Π΅Π³ΠΎ активности
    • 2. 5. Π€ΡƒΠ½ΠΊΡ†ΠΈΠΈ транскрипционного Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° CTCF
      • 2. 5. 1. РСгуляция транскрипции
      • 2. 5. 2. ВзаимодСйствиС CTCF с ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡΠΌΠΈ инсуляторов
      • 2. 5. 3. ΠšΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒ ΠΈΠΌΠΏΡ€ΠΈΠ½Ρ‚ΠΈΠ½Π³Π° гСнСтичСской ΠΈΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΈ
    • 2. 6. Boris
    • 2. 7. CTCF ΠΈ Ρ€Π°Π·Π²ΠΈΡ‚ΠΈΠ΅ Π±ΠΎΠ»Π΅Π·Π½Π΅ΠΉ 37 2.8 ΠœΠ΅Ρ‚ΠΎΠ΄Ρ‹ исслСдования Π”ΠΠš-Π±Π΅Π»ΠΊΠΎΠ²Ρ‹Ρ… взаимодСйствий
    • 2. 9. Π‘Π΄Π²ΠΈΠ³ элСктрофорСтичСской подвиТности Π² ΠΏΠΎΠ»ΠΈΠ°ΠΊΡ€ΠΈΠ»Π°ΠΌΠΈΠ΄Π½ΠΎΠΌ Π³Π΅Π»Π΅
    • 2. 10. ΠœΠ΅Ρ‚ΠΎΠ΄ ΠΈΠΌΠΌΡƒΠ½ΠΎΠΏΡ€Π΅Ρ†ΠΈΠΏΠΈΡ‚Π°Ρ†ΠΈΠΈ Ρ…Ρ€ΠΎΠΌΠ°Ρ‚ΠΈΠ½Π°
    • 2. 11. Π”ΠΠš-Π±Π΅Π»ΠΊΠΎΠ²Ρ‹Π΅ кросс-сшивки (DNA-protein crosslinking assay, DPC)

РасполоТСниС ΠΈ возмоТная Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½Π°Ρ Ρ€ΠΎΠ»ΡŒ участков связывания транскрипционного Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° CTCF Π² локусС 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° (Ρ€Π΅Ρ„Π΅Ρ€Π°Ρ‚, курсовая, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ)

Π‘Ρ‚Ρ€Π΅ΠΌΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹ΠΉ прогрСсс Π² ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½ΠΎΠΉ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ» Ρ€Π°ΡΡˆΠΈΡ„Ρ€ΠΎΠ²Π°Ρ‚ΡŒ ΠΏΠΎΠ»Π½Ρ‹Π΅ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ Π³Π΅Π½ΠΎΠΌΠΎΠ² ΠΌΠ½ΠΎΠ³ΠΈΡ… ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΠΏΠΎΠ·Π²ΠΎΠ½ΠΎΡ‡Π½Ρ‹Ρ… (Lander et.al., 2001). Π’ Ρ‡Π°ΡΡ‚ности, Π±Ρ‹Π»Π° установлСна полная пСрвичная структура чСловСчСского Π³Π΅Π½ΠΎΠΌΠ° ΠΈ ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΎ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ Π² Π³Π΅Π½ΠΎΠΌΠ΅ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° большСй части Π³Π΅Π½ΠΎΠ². Однако, ΡƒΡΡ‚Π°Π½ΠΎΠ²ΠΈΡ‚ΡŒ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΈ Π³Π΅Π½ΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΡ… ΠΏΠ΅Ρ€Π²ΠΈΡ‡Π½ΠΎΠΉ структуры Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ Π΄Π°Π»Π΅ΠΊΠΎ Π½Π΅ Π²ΡΠ΅Π³Π΄Π°. Для Ρ€Π΅ΡˆΠ΅Π½ΠΈΡ этой Π·Π°Π΄Π°Ρ‡ΠΈ трСбуСтся ΠΏΡ€ΠΈΠ²Π»Π΅Ρ‡Π΅Π½ΠΈΠ΅ Π·Π½Π°Π½ΠΈΠΉ ΠΈΠ· Ρ€Π°Π·Π½Ρ‹Ρ… областСй Π½Π°ΡƒΠΊΠΈ: Π±ΠΈΠΎΠΈΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ‚ΠΈΠΊΠΈ, Π³Π΅Π½Π΅Ρ‚ΠΈΠΊΠΈ, Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈ развития, молСкулярной Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈ, Π±ΠΈΠΎΡ…ΠΈΠΌΠΈΠΈ ΠΈ Ρ‚. Π΄. ДостиТСния Π² ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠΈ ΠΏΠ΅Ρ€Π²ΠΈΡ‡Π½ΠΎΠΉ структуры ΠΈ ΠΊΠ°Ρ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠΈ Π³Π΅Π½ΠΎΠΌΠΎΠ² ΠΏΡ€ΠΈΠ²Π΅Π»ΠΈ ΠΊ ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΡŽ Π½ΠΎΠ²ΠΎΠ³ΠΎ направлСния исслСдований — Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠΉ Π³Π΅Π½ΠΎΠΌΠΈΠΊΠΈ, которая Π²ΠΊΠ»ΡŽΡ‡Π°Π΅Ρ‚ Π² ΡΠ΅Π±Ρ Π³Π»Π°Π²Π½Ρ‹ΠΌ ΠΎΠ±Ρ€Π°Π·ΠΎΠΌ ΠΈΠ΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΡŽ, Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°Ρ†ΠΈΡŽ Π² Π³Π΅Π½ΠΎΠΌΠ΅ ΠΈ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½Ρ‹ΠΉ Π°Π½Π°Π»ΠΈΠ· Π½ΠΎΠ²Ρ‹Ρ… Π³Π΅Π½ΠΎΠ².

Π’ Ρ‚ΠΎ ΠΆΠ΅ врСмя Π³Π΅Π½ΠΎΠΌ содСрТит мноТСство нСтранскрибируСмых Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎ Π°ΠΊΡ‚ΠΈΠ²Π½Ρ‹Ρ… элСмСнтов, ΠΎΠ±Π»Π°Π΄Π°ΡŽΡ‰ΠΈΡ… ваТнСйшими рСгуляторными свойствами ΠΈ ΠΈΠΌΠ΅ΡŽΡ‰ΠΈΠΌΠΈ Ρ€Π΅ΡˆΠ°ΡŽΡ‰Π΅Π΅ Π·Π½Π°Ρ‡Π΅Π½ΠΈΠ΅ для Π΅Π³ΠΎ Π½ΠΎΡ€ΠΌΠ°Π»ΡŒΠ½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹. ΠŸΡ€ΠΈΠΌΠ΅Ρ€Π°ΠΌΠΈ Ρ‚Π°ΠΊΠΈΡ… элСмСнтов ΠΌΠΎΠ³ΡƒΡ‚ ΡΠ»ΡƒΠΆΠΈΡ‚ΡŒ энхансСры, Ρ‚Π΅Ρ€ΠΌΠΈΠ½Π°Ρ‚ΠΎΡ€Ρ‹ транскрипции, участки связывания Π”ΠΠš с Ρ€Π΅Π³ΡƒΠ»ΡΡ‚ΠΎΡ€Π½Ρ‹ΠΌΠΈ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ, участки Π½Π°Ρ‡Π°Π»Π° Ρ€Π΅ΠΏΠ»ΠΈΠΊΠ°Ρ†ΠΈΠΈ, мСста ΠΈΠ½Ρ‚Π΅Π³Ρ€Π°Ρ†ΠΈΠΈ рСтроэлСмСнтов ΠΈ Ρ‚. Π΄. Π’ Π±ΠΎΠ»ΡŒΡˆΠΈΠ½ΡΡ‚Π²Π΅ случаСв ΠΏΠΎΠ΄ΠΎΠ±Π½Ρ‹Π΅ структуры Π½Π΅Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ ΠΈΠ΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΡ†ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ, имСя Π΄Π°Π½Π½Ρ‹Π΅ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ ΠΎ Π½ΡƒΠΊΠ»Π΅ΠΎΡ‚ΠΈΠ΄Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ участков Π”ΠΠš, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ ΠΈΡ… ΡΠΎΠ΄Π΅Ρ€ΠΆΠ°Ρ‚. Одним ΠΈΠ· ΡΠΏΠΎΡΠΎΠ±ΠΎΠ² ΠΈΡ… ΠΊΠΎΡ€Ρ€Π΅ΠΊΡ‚Π½ΠΎΠΉ ΠΈΠ΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ являСтся ΡΠΎΠΎΡ‚Π²Π΅Ρ‚ΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠΉ ΡΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Ρ‹ΠΉ, Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½Ρ‹ΠΉ ΠΏΠΎΠ΄Ρ…ΠΎΠ΄. ΠšΠ°Ρ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚Π΅ΠΉ с ΠΈΠ·Π²Π΅ΡΡ‚Π½ΠΎΠΉ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠΉ Ρ€ΠΎΠ»ΡŒΡŽ Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ ΠΎΠ±Π»Π΅Π³Ρ‡Π°Π΅Ρ‚ ΠΏΠΎΠ½ΠΈΠΌΠ°Π½ΠΈΠ΅ ΠΎΠ±Ρ‰Π΅ΠΉ ΠΎΡ€Π³Π°Π½ΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΈ ΠΎΡΠ½ΠΎΠ²Π½Ρ‹Ρ… ΠΏΡ€ΠΈΠ½Ρ†ΠΈΠΏΠΎΠ² рСгуляции Ρ€Π°Π±ΠΎΡ‚Ρ‹ Π³Π΅Π½ΠΎΠΌΠ° ΠΊΠ°ΠΊ Ρ†Π΅Π»ΠΎΠ³ΠΎ.

Π˜Π·Π²Π΅ΡΡ‚Π½ΠΎ, Ρ‡Ρ‚ΠΎ ΠΌΠ½ΠΎΠ³ΠΈΠ΅ Π±Π΅Π»ΠΊΠΈ способны спСцифичСски ΡΠ²ΡΠ·Ρ‹Π²Π°Ρ‚ΡŒΡΡ с Ρ‚Π΅ΠΌΠΈ ΠΈΠ»ΠΈ ΠΈΠ½Ρ‹ΠΌΠΈ участками Π”ΠΠš. БвязываниС ядСрных Π±Π΅Π»ΠΊΠΎΠ² с Ρ€Π΅Π³ΡƒΠ»ΡΡ‚ΠΎΡ€Π½Ρ‹ΠΌΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡΠΌΠΈ Π”ΠΠš являСтся Π³Π»Π°Π²Π½Ρ‹ΠΌ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΎΠΌ рСгуляции экспрСссии Ρƒ ΡΡƒΠΊΠ°Ρ€ΠΈΠΎΡ‚. Π‘Ρ€Π΅Π΄ΠΈ Π±Π΅Π»ΠΊΠΎΠ², Π²ΠΎΠ²Π»Π΅Ρ‡Ρ‘Π½Π½Ρ‹Ρ… Π² ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡŽ эукариотичСских Π³Π΅Π½ΠΎΠ², ΡΡƒΡ‰Π΅ΡΡ‚Π²ΡƒΡŽΡ‚ ΠΌΠ½ΠΎΠ³ΠΎΡ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½Ρ‹Π΅ Π±Π΅Π»ΠΊΠΈ, Π΄Π΅ΠΉΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠ΅ Π½Π° Ρ€Π°Π·Π½Ρ‹Ρ… этапах экспрСссии Π³Π΅Π½ΠΎΠ²: ΠΏΡ€ΠΈ ΠΈΠ½ΠΈΡ†ΠΈΠ°Ρ†ΠΈΠΈ ΠΈ ΡΠ»ΠΎΠ½Π³Π°Ρ†ΠΈΠΈ транскрипции, трансляции.

Π¦Π΅Π»ΠΈ ΠΈ Π·Π°Π΄Π°Ρ‡ΠΈ Ρ€Π°Π±ΠΎΡ‚Ρ‹.

ЦСлью диссСртационной Ρ€Π°Π±ΠΎΡ‚Ρ‹ являСтся идСнтификация сайтов связывания транскрипционного Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° CTCF Π² Π»ΠΎΠΊΡƒΡΠ΅ 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°, Π΄Π»ΠΈΠ½ΠΎΠΉ ΠΎΠΊΠΎΠ»ΠΎ 1 ΠΌΠ»Π½.ΠΏ.Π½., находящСгося ΠΌΠ΅ΠΆΠ΄Ρƒ ΠΌΠ°Ρ€ΠΊΠ΅Ρ€Π°ΠΌΠΈ FXYD5 ΠΈ Π‘ΠΎΡ…7А1. Π­Ρ‚ΠΎΡ‚ локус содСрТит Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ число извСстных Π³Π΅Π½ΠΎΠ² ΠΈ Π΅Π³ΠΎ нуклСотидная ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ ΠΏΠΎΠ»Π½ΠΎΡΡ‚ΡŒΡŽ установлСна, Ρ‡Ρ‚ΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ‚, ΠΊΠ°ΠΊ ΠΊΠ°Ρ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ всС ΠΎΡ‚ΠΎΠ±Ρ€Π°Π½Π½Ρ‹Π΅ элСмСнты с Π±ΠΎΠ»ΡŒΡˆΠΎΠΉ Ρ‚ΠΎΡ‡Π½ΠΎΡΡ‚ΡŒΡŽ, Ρ‚Π°ΠΊ ΠΈ ΡΠ΄Π΅Π»Π°Ρ‚ΡŒ Π²Ρ‹Π²ΠΎΠ΄Ρ‹ ΠΎ Π²Π·Π°ΠΈΠΌΠ½ΠΎΠΌ располоТСнии Π±Π΅Π»ΠΎΠΊ-ΡΠ²ΡΠ·Ρ‹Π²Π°ΡŽΡ‰ΠΈΡ… элСмСнтов ΠΈ Π³Π΅Π½ΠΎΠ² ΠΈ ΠΈΡ… Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΉ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠΉ взаимосвязи.

Π‘Ρ‹Π»ΠΈ поставлСны ΡΠ»Π΅Π΄ΡƒΡŽΡ‰ΠΈΠ΅ ΡΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Ρ‹Π΅ Π·Π°Π΄Π°Ρ‡ΠΈ:

— Π²Ρ‹ΡΠ²ΠΈΡ‚ΡŒ с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° сдвига элСктрофорСтичСской подвиТности (EMSA) участки связывания Π±Π΅Π»ΠΊΠ° CTCF Π² Π»ΠΎΠΊΡƒΡΠ΅ 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΌΠ΅ΠΆΠ΄Ρƒ ΠΌΠ°Ρ€ΠΊΡ‘Ρ€Π°ΠΌΠΈ FXYD5 ΠΈ Π‘ΠΎΡ…7А1;

— ΠΊΠ»ΠΎΠ½ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ ΠΈ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ участки Π”ΠΠš, ΡΠ²ΡΠ·Ρ‹Π²Π°ΡŽΡ‰ΠΈΠ΅ΡΡ с Π±Π΅Π»ΠΊΠΎΠΌ CTCF;

— Π²Ρ‹ΡΠ²ΠΈΡ‚ΡŒ Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚Ρ‹ Π”ΠΠš, ΡΠ²ΡΠ·Ρ‹Π²Π°ΡŽΡ‰ΠΈΠ΅ΡΡ с Π±Π΅Π»ΠΊΠΎΠΌ CTCF in vivo с ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΈΠΌΠΌΡƒΠ½ΠΎΠΏΡ€Π΅Ρ†ΠΈΠΏΠΈΡ‚Π°Ρ†ΠΈΠΈ Ρ…Ρ€ΠΎΠΌΠ°Ρ‚ΠΈΠ½Π° (ChlP-assay), ΠΈ ΡΡ€Π°Π²Π½ΠΈΡ‚ΡŒ ΠΈΡ… Ρ Π²Ρ‹Π΄Π΅Π»Π΅Π½Π½Ρ‹ΠΌΠΈ Π² ΡΠΈΡΡ‚Π΅ΠΌΠ΅ in vitro;

— ΠΏΠΎΡΡ‚Ρ€ΠΎΠΈΡ‚ΡŒ ΠΊΠ°Ρ€Ρ‚Ρƒ распрСдСлСния сайтов связывания CTCF Π² Π»ΠΎΠΊΡƒΡΠ΅ 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΌΠ΅ΠΆΠ΄Ρƒ ΠΌΠ°Ρ€ΠΊΡ‘Ρ€Π°ΠΌΠΈ FXYD5 ΠΈ Π‘ΠΎΡ…7А1.

2.0Π±Π·ΠΎΡ€ Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹.

Π’Ρ‹Π²ΠΎΠ΄Ρ‹.

1. Π‘ ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚Π°Π½Π½ΠΎΠ³ΠΎ Π½Π°ΠΌΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° Π΄Π²ΡƒΠΌΠ΅Ρ€Π½ΠΎΠ³ΠΎ EMSA Π±Ρ‹Π»Π° ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π° Π±ΠΈΠ±Π»ΠΈΠΎΡ‚Π΅ΠΊΠ° Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° локуса FXYD5-COX7A1 Π΄Π»ΠΈΠ½ΠΎΠΉ ΠΎΠ΄ΠΈΠ½ ΠΌΠΈΠ»Π»ΠΈΠΎΠ½ ΠΏΠ°Ρ€ оснований, способных ΡΠ²ΡΠ·Ρ‹Π²Π°Ρ‚ΡŒΡΡ с Ρ‚ранскрипционным Ρ„Π°ΠΊΡ‚ΠΎΡ€ΠΎΠΌ CTCF.

2. Π’ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Π΅ Π°Π½Π°Π»ΠΈΠ·Π° Π±ΠΈΠ±Π»ΠΈΠΎΡ‚Π΅ΠΊΠΈ, выявлСны ΠΈ ΠΊΠ°Ρ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½Ρ‹ Π΄Π΅ΡΡΡ‚ΡŒ участков связывания CTCF Π² Π»ΠΎΠΊΡƒΡΠ΅ 19 хромосомы Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°.

3. ΠŸΡ€ΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· располоТСния ΠΊΠ°Ρ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚Π΅ΠΉ ΠΎΡ‚Π½ΠΎΡΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ Π³Π΅Π½ΠΎΠ² локуса FXYD5-COX7A1.Показано, Ρ‡Ρ‚ΠΎ сСмь ΠΈΠ· Π΄Π΅ΡΡΡ‚ΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚Π΅ΠΉ располоТСны Π²Π½ΡƒΡ‚Ρ€ΠΈ Π³Π΅Π½ΠΎΠ² (прСимущСствСнно Π² ΠΈΠ½Ρ‚Ρ€ΠΎΠ½Π°Ρ…), Ρ‚Ρ€ΠΈ располоТСны Π² ΠΌΠ΅ΠΆΠ³Π΅Π½Π½Ρ‹Ρ… участках локуса.

4. ΠœΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ΠΈΠΌΠΌΡƒΠ½ΠΎΠΏΡ€Π΅Ρ†ΠΈΠΏΠΈΡ‚Π°Ρ†ΠΈΠΈ Ρ…Ρ€ΠΎΠΌΠ°Ρ‚ΠΈΠ½Π° Π΄ΠΎΠΊΠ°Π·Π°Π½ΠΎ спСцифичСскоС связываниС всСх дСсяти ΠΊΠ°Ρ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚Π΅ΠΉ с Ρ‚ранскрипционным Ρ„Π°ΠΊΡ‚ΠΎΡ€ΠΎΠΌ CTCF in vivo.

5. Показано, Ρ‡Ρ‚ΠΎ ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½Π½Ρ‹Π΅ Ρ€Π°Π½Π΅Π΅ сСмь ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚Π΅ΠΉ, ΠΎΠ±Π»Π°Π΄Π°ΡŽΡ‰ΠΈΡ… инсуляторной Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒΡŽ, способны ΡΠ²ΡΠ·Ρ‹Π²Π°Ρ‚ΡŒΡΡ с Ρ‚ранскрипционным Ρ„Π°ΠΊΡ‚ΠΎΡ€ΠΎΠΌ CTCF in vivo.

Π― Ρ…ΠΎΡ‡Ρƒ Π²Ρ‹Ρ€Π°Π·ΠΈΡ‚ΡŒ ΡΠ°ΠΌΡƒΡŽ ΠΈΡΠΊΡ€Π΅Π½Π½ΡŽΡŽ ΠΏΡ€ΠΈΠ·Π½Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ своСму Π½Π°ΡƒΡ‡Π½ΠΎΠΌΡƒ Ρ€ΡƒΠΊΠΎΠ²ΠΎΠ΄ΠΈΡ‚Π΅Π»ΡŽ ΠΊ.Π±.Π½. Π‘Π΅Ρ€Π³Π΅ΠΉ Борисовичу Акопову Π·Π° ΡΠΎΠ²Π΅Ρ‚Ρ‹, ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠΊΡƒ ΠΈ ΠΏΠΎΠΌΠΎΡ‰ΡŒ Π½Π° ΠΊΠ°ΠΆΠ΄ΠΎΠΌ этапС Ρ€Π°Π±ΠΎΡ‚Ρ‹.

Π’Ρ‹Ρ€Π°ΠΆΠ°ΡŽ Π³Π»ΡƒΠ±ΠΎΠΊΡƒΡŽ Π±Π»Π°Π³ΠΎΠ΄Π°Ρ€Π½ΠΎΡΡ‚ΡŒ Π·Π°Π²Π΅Π΄ΡƒΡ‰Π΅ΠΌΡƒ Π›Π°Π±ΠΎΡ€Π°Ρ‚ΠΎΡ€ΠΈΠ΅ΠΉ Π‘Ρ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Ρ‹ ΠΈ Π€ΡƒΠ½ΠΊΡ†ΠΈΠΉ Π“Π΅Π½ΠΎΠ² Π§Π΅Π»ΠΎΠ²Π΅ΠΊΠ° Π°ΠΊΠ°Π΄Π΅ΠΌΠΈΠΊΡƒ Π•Π²Π³Π΅Π½ΠΈΡŽ Π”Π°Π²ΠΈΠ΄ΠΎΠ²ΠΈΡ‡Ρƒ Π‘Π²Π΅Ρ€Π΄Π»ΠΎΠ²Ρƒ, Π·Π°ΠΌΠ΅ΡΡ‚ΠΈΡ‚Π΅Π»ΡŽ Π·Π°Π²Π΅Π΄ΡƒΡŽΡ‰Π΅Π³ΠΎ Π»Π°Π±ΠΎΡ€Π°Ρ‚ΠΎΡ€ΠΈΠ΅ΠΉ Π“Π°Π»ΠΈΠ½Π΅ Π‘Π΅Ρ€Π³Π΅Π΅Π²Π½Π΅ ΠœΠΎΠ½Π°ΡΡ‚Ρ‹Ρ€ΡΠΊΠΎΠΉ, Π›ΡŒΠ²Ρƒ Π“Ρ€ΠΈΠ³ΠΎΡ€ΡŒΠ΅Π²ΠΈΡ‡Ρƒ НиколаСву, Π° Ρ‚Π°ΠΊΠΆΠ΅ прСкрасному ΠΊΠΎΠ»Π»Π΅ΠΊΡ‚ΠΈΠ²Ρƒ Π»Π°Π±ΠΎΡ€Π°Ρ‚ΠΎΡ€ΠΈΠΈ Π·Π° Π΄Ρ€ΡƒΠΆΠ΅ΡΠΊΠΎΠ΅ ΠΈ Π²Π½ΠΈΠΌΠ°Ρ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ ΠΎΡ‚Π½ΠΎΡˆΠ΅Π½ΠΈΠ΅. Π‘Π΅Π· ΠΈΡ… ΡΠΎΠ²Π΅Ρ‚ΠΎΠ² ΠΈ Π΄Ρ€ΡƒΠΆΠ΅ΡΠΊΠΎΠ³ΠΎ участия Π² Ρ€Π°Π±ΠΎΡ‚Π΅ Π΅Π΅ Π²Ρ‹ΠΏΠΎΠ»Π½Π΅Π½ΠΈΠ΅ Π±Ρ‹Π»ΠΎ Π±Ρ‹ Π½Π΅Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ.

ΠŸΠΎΠΊΠ°Π·Π°Ρ‚ΡŒ вСсь тСкст

Бписок Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹

  1. «ΠΠ½Π°Π»ΠΈΠ· Π³Π΅Π½ΠΎΠΌΠ°. ΠœΠ΅Ρ‚ΠΎΠ΄Ρ‹». Π‘Π±ΠΎΡ€Π½ΠΈΠΊ ΠΏΠΎΠ΄ Ρ€Π΅Π΄. ДСйвис, К., Π‘Π°Π½Ρ‚ΠΈΠ½Π³, Π“., ΠšΠ°Π½Ρ‚ΠΎΡ€, Π§., Коллинз Π€. ΠΈ Π΄Ρ€. ΠŸΠ΅Ρ€. Ρ Π°Π½Π³Π». ΠΏΠΎΠ΄ Ρ€Π΅Π΄. П. Π›. Иванова. М.: ΠœΠΈΡ€, 1990,247с.
  2. Π›.И. «Π­ΠΊΡΠΏΡ€Π΅ΡΡΠΈΡ Π³Π΅Π½ΠΎΠ²». Москва, Наука, 2000, 830 стр.
  3. Adams D. van der Weyden L., Kovacic. A., Lovicu F., Copeland N., Gillbert D., Jenkins N., Ioannou P., Morris Π’., (2000). Chromosome localization and characterization of the mouse and human zinc finger protein 265 gene. Cytogenet. Cell. Genet., 88, 68−73
  4. Ansari, S. A., Safak, M., Gallia, G. L., Sawaya, Π’. E., Amini, S., and Khalili, K.(1999). Interaction of YB-1 with human immunodeficiency virus type 1 Tat and TAR RNA modulates viral promoter activity. J. Gen. Virol. 80,2629−2638
  5. Antes, T.J., Namciu, S.J., Fournier, R.E. and Levy-Wilson, B. (2001). The 5' boundary of the human apolipoprotein Π’ chromatin domain in intestinal cells. Biochemistry 40(23), 6731−6742
  6. Antonio L. Amelio, Peterjon K. McAnany, and David C. Bloom (2006). Virus Type 1 Latency-Associated Transcript Region Binds CCCTC-Binding Factor and Displays Enhancer-Blocking and Silencing Activities. J. Virol., 80, 2358−2368
  7. Arnold, R. Burcin, M. Kaiser, B. Muller, M. Renkawitz, R. (1996). DNA bending by the silencer protein NePl is modulated by TR and RXR. Nucleic Acids Res. Jul 15- 24(14): 2640−2647
  8. A., Steiner C., Kohne A.C., Renkawitz R. (1990). Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site. Cell, 61,505−514
  9. Bell A.C. and Felsenfeld (1999). Stopped at the border: boundaries and insulators. Curr. Opin. Genet. Dev., 9, 191−198
  10. Bell A.C. and Felsenfeld G.(2000). Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature, 405, 482−485
  11. Bi X. and Broach J.(2001). Chromosomal boundaries in S.cerevisiae. Curr.Opin.Genet.Dev., 11,199−204
  12. Bigler, J. Eisenman, R.N. (1995) «Novel location and function of a thyroid hormone response element». EMBO J. Nov 15- 14(22): 5710−23
  13. E., Kadonaga J. (1998). Going the distance: a current view of enhanser action. Science 281, 60−63
  14. Buck M. and Lieb J. (2004). Chip-chip: considerations for the design, analysisand aplication of the genome-wide chromatin immunoprecipitationexperiments. Genomics 83: 349−360
  15. Burcin, M. et al. (1997). Negative protein 1, which is required for function of the chicken lysozyme gene silencer in conjunction with hormone receptors, is identical to the multivalent zinc finger repressor CTCF. Mol. Cell. Biol. 17, 1281−1288.
  16. Burke, L.J. Zhang, R. Lutz, M. Renkawitz, R. (2002) «The thyroid hormone receptor and the insulator protein CTCF: two different factors with overlapping functions». J Steroid Biochem Mol Biol. Dec- 83(1−5): 49−57
  17. Carter D., Chakalova L., Osborne C., Dai Y., Fraser P.(2002). Long range chromatin regulatory in vivo. Nat.Genet.32 623−26
  18. J. R. (1998) Theoretical studies on the mobility-shift assay of protein-DNA complexes, Electrophoresis, Vol. 19, No. 2, 127−141
  19. J. E., Fink M., Kaltoft K. (1986). On the use of ultraviolet light to study protein-DNA cross-linking for genomewide binding microarray. Methods 31: 90−95
  20. Chau M.C., Zhang X.Y., McMahon S.B., Lieberman P.M. (2006). Regulation of Epstein-Barr Virus latency type by the chromatin boundary factor CTCF. J Vir., 80 (12), 5723−5732
  21. Chen N.N. and Khalili, K. (1995) Transcriptional regulation of human JC polyomavirus promoters by cellular proteins YB-1 and Pur a in glial cells. J. Virol., 69, 5843−5848
  22. Chen S. and Corces V.G. (2001). The gypsy insulator of Drosophila affects chromatin structure in a directional manner. Genetics, v.159, 1649−1658
  23. Chernov I.P., Akopov S.B., Nikolaev L. G, and Sverdlov E.D. (2006). Identification and mapping of DNA binding proteins target sequences in long genomic regions by two-dimensional EMSA. BioTechniques 41:90−96
  24. Chernukhin I., Shamsuddin S., Robinson A., Carne A., Paul A., El-Kady A., Lobanenkov V., and Klenova E. (2000). Physical and Functional Interaction between
  25. Two Pluripotent Proteins, the Y-box DNA/RNA-binding Factor, YB-1, and the Multivalent Zinc Finger Factor CTCF. Journal of Biological chemistry Vol. 275, No. 38,29 915−29 921.
  26. Chodosh L. A., Carthew R. W., and Sharp P. A. (1986). A single polypeptide possesses the binding and transcription activities of the adenovirus major late transcription factor, Mol Cell Biol, Vol. 6, β„–. 12,4723−4733
  27. Chung, J.H., Whiteley, M. and Felsenfeld, G. (1993). A 5' element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74(3), 505−514
  28. P.R. (2003). Nongenic trascription, gene regulation and action at a distance. J. CellScL, 116,4483−4491
  29. Das P.M., Ramachandran K., van Wert J., Singal R. (2004). Chromatin immunoprecipitation assay. BioTechiques 37: 961−969
  30. Davies, R.C., Calvio, C., Bratt, E., Larsson, S.H., Lamond, A.I., Hastie, N.D. (1998) «WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes.» Genes & Dev. 12: 3217 3225.
  31. Defossez P. and E. Gilson (2002). The vertebrate protein CTCF functions as an insulator in Saccharomyces cerevisiae. Nucleic Acids Research, 30: 5136−5141
  32. M.D., Chernukhin I.V., Bigas A., Klenova E.M., Leon J. (1999). Differential expression and phoshorylation of CTCF, a c-myc trascriptional regulator, during differentiation of human myeloid cells. FEBS Letters 444 5−10
  33. DePinho, R.A. (1998). Transcriptional repression: The cancer-chromatin connection." Nature 391, 533 534
  34. Dignam J. D., Lebovitz R. M., and Roeder R. G. (1983). Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei, Nucleic Acids Research, Vol. 11, β„–. 5, 1475−1489
  35. Drueppel, L. Pfleiderer, K. Schmidt, A. Hillen, W. Berens, C. (2004) «A short autonomous repression motif is located within the N-terminal domain of CTCF». FEBS Lett. Aug 13- 572(1−3): 154−8
  36. Dunaway M., Hwang J., Xiong M. and Yuen H.L. (1997). The activity of the scs and scs' insulator elements is not depend on chromosomal context. Molecular and Cellular Biology, 17,182−189
  37. Dunn K.L. and Davie J.R. (2003).The many roles of the trascriptional regulator CTCF. Biochemical Cell Biology, 81, 161−167
  38. El-Kady, A. Klenova, E. (2005) «Regulation of the transcription factor, CTCF, by phosphorylation with protein kinase CK2″. FEBS Lett. Feb 28- 579 (6): 1424−34
  39. N., West A. Felsenfeld G., Bartolamei M. (2004). Antagonism between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpG mutations. Nat.Genet., 36, 883−888
  40. Farrell, C.M. West, A.G. Felsenfeld, G. (2002) „Conserved CTCF insulator elements flank the mouse and human beta-globin loci“. Mol Cell Biol. Jun- 22 (11): 3820−31
  41. A., Stein P., Svoboda P., Schultz R., Bartolomei M. (2004). Trasgenenic RNAi reveals essential function for CTCF in H19 gene imprinting. Science 303, 238−240
  42. Feng, J., Funk, W. D» Wang, S.S., Weinrich, S.L., Avilion, A.A., Chiu, C.P., Adams, R.R., Chang, E., Allsopp, R.C. and Yu, J. (1995) The RNA component of human telomerase. Science, 269, 1236−1241.
  43. Filippova, G. et al. (1996). «An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes.» Moi. Cell. Biol. 16, 28 022 813.
  44. Filippova G.N., Thienes CP, Penn BH, Cho DH, Hu YJ, Moore JM, Klesert TR, Lobanenkov VV, Tapscott SJ (2001). CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat Genet 28: 335−343
  45. Filippova, Galina N. Qi, Chen-Feng, Ulmer, J. E. et al. (2002). «Tumor-associated Zinc Finger Mutations in the CTCF Transcription Factor Selectively Alter Its DNA-binding Specificity.» Cancer Res. 62:48 52.
  46. Fleischer, T.C., Yun, U.J. Ayer, D.E. (2003) «Identification and characterization of three new components of the mSin3A corepressor complex». Mol Cell Biol. May- 23(10): 3456−67
  47. Fox A.H., Chu Liew, Melissa Holmes, Kasper Kowalski, Joel Mackay and Merlin Crossley (1999). Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers. EMBO18,2812−2822
  48. J., Frederics W., Jensen D., Speicher D., Huang X., Neilson E., Rauscher F., (1996). KAP-1, a novel corepressor for the highly conserved KRAB repression domain. Genes Dev., 10,2067−2078
  49. M., Crothers D.M. (1981). Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res., Dec- 9: 6505 -6525
  50. Gaszner M. and Felsenfeld G. (2006). Insulators: exploiting transcriptional and epigenetic mechanisms. Nature Reviews Genetics 8, 703−713
  51. Gerasimova T.I. and Corces V.G. (2001). Chromatin insulators and boundaries: effects on transcription and nuclear organization. Annu. Rev. Genet, v.35, 193−208
  52. Geyer, P.K. and Corces, V.G. (1992). DNA position-specific repression of transcription by a Drosophila zinc finger protein. Genes Dev 6(10), 1865−1873
  53. Geyer, P.K., Green, M.M. and Corces, V.G. (1990). Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: the molecular basis of transvection in Drosophila. EmboJ 9(7), 2247−2256
  54. Gombert W.M., Farris S.D., Rubio E.D., Morey-Rosler K.M., Schubach W.H., Krumm (2003). The c-myc insulator element and matrix attachment regions define the c-myc chromosomal domain. MOLECULAR AND CELLULAR BIOLOGY, Vol. 23, № 24, 9338−9348
  55. Grondin Π’., Bazinet M., Aubry (1996). The KRAB zinc finger gene ZNF74 encodes an RNA-binding protein tightly associated with the nuclear matrix. J. Biol. Chem., 271, 15 458−15 467
  56. Grondin, Π’., Cote, F., Bazinet, M" Vincent, M., Aubry, M. (1997) «Direct Interaction of the KRAB/Cys2-His2 Zinc Finger Protein ZNF74 with a Hyperphosphorylated Form of the RNA Polymerase II Largest Subunit.» J. Biol. Chem. 272: 27 877 27 885.
  57. Ghosh, D., Gerasimova, T.I. and Corces, V.G. (2001). Interactions between the Su (Hw) and Mod (mdg4) proteins required for gypsy insulator function. Embo J 20(10), 2518−2527
  58. Hammilton Π’., Borel. F., Romaniuk P., (1998). Comparison of the DNA binding characteristics of the related zinc finger proteins WT1 and EGR1. Biochemistry, 37, 2051−2058
  59. Hammes A., Guo J., Lutsch G., Leheste J, Landrock D., Ziegler U., Gubler M., Schedl A., (2001). Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation. Cell., 106, 319−329
  60. Hark, A.T., Schoenherr, C.J., Katz, D.J., Ingram, R.S., Levorse, J.M., Tilghman, S.M. (2000) «CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus». Nature 405 (6785): 486−489.
  61. Heng, S. A. Krawetz, W. Lu, S. Bremer, G. Liu, C. J. Ye, (2001). Re-defining the chromatin loop domain, Cytogenet Cell Genet. 93 155−161
  62. Horikawa, I. and Barrett, J.C. (2003) Transcriptional regulation of the telomerase hTERT gene as a target for cellular and viral oncogenic mechanisms. Carcinogenesis, 24, 1167−1176
  63. N. Kanduri Π‘., Dell G., Ward R., Mukhopadhya et.al. (2001). CpG methylation regulates the M2/H19 insulator. Current Biology 11, 1128−1130
  64. Inoue, H., Nojima, H. and Okayama, H. (1990). High efficiency transformation of Escherichia coli with plasmids. Gene 96(1), 23−28
  65. Ishihara and Sasaki (2002). An evolutional conserved putative insulator element near the 3' boundary of the imprinted Igf2/H19 domain. Human Molecular Genetics, v. 11 (14), 1627−1636
  66. Johnson P.E., McKnight S.L. (1989). Eukaryotic transcriptional regulatory proteins. Annu Rev. Biochem 58: 799−839
  67. Kadonaga J. and Tjian R. (1986). Affinity Purification of Sequence-Specific DNA Binding Proteins. PNAS, 83, 5889−5893
  68. , J.T. (2004). «Regulation of RNA polymerase II transcription by sequence-specific DNA binding factors.» Cell 116(2): 247−257.
  69. Kanduri, C. et al. (2000). «The 5'-flank of the murine HI 9 gene in an unusual chromatin conformation unidirectionally blocks enhancer-promoter communication.» Curr. Biol. 10,449157.
  70. Kellum, R. and Schedl, P. (1992). A group of scs elements function as domain boundaries in an enhancer-blocking assay. Mo I Cell Biol 12(5), 2424−243
  71. Kim, N.W., Piatyszek, M. A" Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L., Coviello, G. M, Wright, W.E., Weinrich, S.L. and Shay, J.W. (1994) Specific association of human telomerase activity with immortal cells and cancer. Science, 266, 2011−2015
  72. E., Morse H., Ohlsson R., Lobanenkov V. V. (2002). The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer, Semin Cancer Biol, Vol. 579, β„–. 6, 399−414.
  73. Klenova E., Lobanenkova V., Ohlosson (2004). The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome wide. Genome research, 14, 1594−1602
  74. Kohne AC, Baniahmad A, Renkawitz R.(1993) NePl. A ubiquitous transcription factor synergizes with v-ERBA in transcriptional silencing. Mol Biol. 232(3):747−55
  75. G. W. Konat (1996). Chromatin structure and transcriptional activity of MAG gene. Acta Neurobiol Exp. 56: 281−285
  76. N. J. Kubat, R. K. Tran, P. McAnany, and D. C. Bloom (2004).The Herpes Simplex Virus Type 1 Latency-Associated Transcript (LAT) Enhancer/rcr Is Hyperacetylated during Latency Independently of LAT Transcription J. Virol. 78:1139−1149.
  77. Kuhn E.J. and Geyer, P.K. (2003). Genomic insulators: connecting properties to mechanism. Curr Opin Cell Biol 15(3), 259−265
  78. , M., Marshall R., Arif L., Sommerville J., (2000). C4SR, a novel zinc-finger protein with SR-repeats, is expressed during early development of Xenopus. Gene, 256,293−302
  79. Ladomery, M. and Dellaire, G. (2002) «Multifunctional zinc finger proteins in development and disease.» Ann Hum Genet. 2002 66(Pt 5−6):331−42.
  80. Ladomery M. and Sommerville, J. (1995). A role for Y-box proteins in cell proliferation. Bioessays, 17, 9−11.
  81. Laemmli U.K. and Favre M., (1973) J.Mol.Biol., 80, 601−613
  82. J., Dyson H., Wright P., (2000). Molecular basis for modulation of biological function by alternative splicing of the Wilms' tumor suppressor protein. PNAS, 97, 11 932−11 935
  83. Laybourn, P.J., Kadonaga, J.T. (1992). «Threshold phenomena and long-distance activation of transcription by RNA polymerase II.» Science 257(5077): 1682−5.
  84. Li, W. W., Hsiung, Y., Wong, V., Galvin, K., Zhou, Y., Shi, Y., and Lee, A. S. (1997). Suppression of grp78 core promoter element-mediated stress induction by the dbpA and dbpB (YB-1) cold shock domain proteins. Mol. Cell. Biol. 17, 61−68
  85. Li, H., Cao, Y., Berndt, M.C., Funder, J.W. and Liu, J.P. (1999) Molecular interactions between telomerase and the tumor suppressor protein p53 in vitro. Oncogene, 18, 6785−6794
  86. Loeb, D.D., Mack, A.A., Tian, R. (2002). «A Secondary Structure That Contains the 5' and 3' Splice Sites Suppresses Splicing of Duck Hepatitis Π’ Virus Pregenomic RNA.» J. Virol. 76:10 195 10 202.
  87. F., Yusufzau T.M., Fenselfend G. (2004). Both CTCF-dependent and -independent insulators are found between the mouse T-cell receptor a and Dadl genes. J. Biol. Chem., 279: 25 381 25 389
  88. Manley J. L. Fire, A., Samuels, M. & Sharp, P. A. (1983). In vitro transcription: whole-cell extract. Methods Enzymol, Vol. 101, 568−582
  89. Melnikova L., Gause M. and Georgiev P. (2002). The gypsy insulators flanking yellow enhancers do not form a separate transcriptional domain in Drosophila melanogaster: the enhancers can activate an isolated yellow promoter. Genetics, 160, 1549−1560
  90. Mertens P.R., Alfonso-Jaume, M.A., Steinmann, K. and Lovett, D.H. (1998) A synergistic interaction of transcription factors AP2 and YB-1 regulates gelatinase A enhancer-dependent transcription. J. Biol. Chem., 273, 32 957−32 965
  91. G.B. (1989). The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell, 59:521−529
  92. R. H. (2003). Getting into chromatin: how do transcription factors get past the histones. Biochem Cell Biol, Vol. 81, β„–. 3, 101−112
  93. Nagaya S., Yoshida K., Kato K., Aksaka K. and Shinmyo (2001). An insulator element from the sea urchin Hemicentrotus pulcherrimus suppresses variation in transgene expression in cultured tobacco cells. Mol Gen Genomics, v.265, 405−413
  94. Nakano M., Yoshiura К., Oikawa M., Miyoshi О., Yamada К., Kondo S., Miwa N., Soeda E., Jinno Y., Fujii T, Niikawa N., (1998). Identification, characterization and mapping of the human ZIS (zinc finger, splicing gene). Gene, 225, 59−65
  95. J., Gibson Π’., Vesque C., Charnay P. (1991). Base sequence discrimination by zinc-finger DNA-binding domains. Nature, 349,175−178
  96. Nikolaev L.G. Glotov BO, Beliavskii AV, Levin AV. (1987). Characteristics of the protein specifically binding to the major late promoter of adenovirus type 2, Dokl AkadNaukSSSR., Vol. 294, β„–. 5, 1251−1254
  97. L.G. Glotov B.O., Belyavsky A.V., Grachev S.A., Levin A.V. (1988). Identification of sequence-specific DNA-binding factors by label transfer: application to the adenovirus-2 major late promoter, Nucleic Acids Research, Vol. 16, № 2, 519−535
  98. Orlando, 2000. Mapping chromosomal proteins in vivo by formaldehyde-crosslinked-chromatin immunoprecipitation, Trends Biochem Sci. 25 99−104
  99. Ogbourne, S. and Antalis, T.M. (1998). Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes. Biochem J331(Pt 1), 1−14.
  100. Ohlsson, R., Renkawitz, R., Lobanenkov, V. (2001). «CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease.» Trends Genet 17(9): 520−527.
  101. К Oshiman, M Maeda, S Tamura, S Kaya, S Mahmood, MA Reuben, LS Lasater, G Sachs, and M Futai (1991). The rat H+/K (+)-ATPase beta subunit gene and recognition of its control region by gastric DNA binding protein. J. Biol. Chem., 266:21 584−21 588
  102. Papavassiliou A. and Silverstein S.(1990) Characterization of DNA-protein complex formation in nuclear extracts with a sequence from the herpes simplex virus. J.Biol.Chem. 265- 1648−1657
  103. Park К., AtchinsonM. (1991). Isolation of a candidate repressor/activator, NF-E1, that binds to the immunoglobulin kappa 3'enhancer and the immunoglobulin heavy-chain mu El site. PNAS, 88, 809−817
  104. Percec I. and Bartolomei M. (2002). Do X Chromosomes Set Boundaries. Science, Vol. 295 β„–. 5553, 287−288.
  105. J.C., Andrews L.G., Tollefsbol Π’.О. (2001). Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene- 269: 1−12
  106. Pritchard-Jones K., Fleming S., Davidson D., Bickmore W., Porteous D., Gosden
  107. C., Bard J., Buckler A., Pelletier J., Housman D., van Heyningen V., Hastie N. (1990). The candidate Wilms' tumor gene is involved in genitourinary development. Nature 346: 194−197
  108. Quitschke, W.W. Taheny, M.J., Fochtmann, L.J., Vostrov, A.A. (2000). «Differential effect of zinc finger deletions on the binding of CTCF to thepromoter of the amyloid precursor protein gene.» Nucleic Acids Res. 28, 3370−3378
  109. Qi C., Martensson A., Mattioli M., Dalla-Favera R., Lobanenkov V., and. Morse III H. (2002). CTCF functions as a critical regulator of cell-cycle arrest and death after ligation of the Π’ cell receptor on immature Π’ cells, PNAS, Vol. 100, № 2, 633 638.
  110. Rand E., Ben-Porath I., Keshet I., Cedar H. (2004).CTCF elements direct allele-specific undermethylation at the imprinted H19 locus. Current biology, 14 (11):1007−1012
  111. Rasko J., Klenova E., Javier Leon J., Galina N. Filippova G., Dmitri I. Loukinov
  112. Raj G.V., Safak, M., MacDonald, G.H. and Khalili, K. (1996) Transcriptional regulation of human polyomavirus JC: evidence for a functional interaction between RelA (p65) and the Y-box-binding protein, YB-1. J. Virol., 70, 5944−5953
  113. Recillas-Targa, F., Bell, A.C. and Felsenfeld, G. (1999). Positional enhancer-blocking activity of the chicken beta-globin insulator in transiently transfected cells. PNAS USA 96(25), 14 354−14 359
  114. Recillas-Targa, F., Valadez-Graham, V. and Farrell, C.M. (2004). Prospects and implications of using chromatin insulators in gene therapy and transgenesis. Bioessays 26(7), 796−807
  115. Renaud S., Loukinov D., Bosman F., Lobanenkov V., Jean Benhattar (2005). CTCF binds the proximal exonic region of hTERT and inhibits its transcription. Nucleic Acids Research, 2005, Vol. 33, No. 21, 6850−6860
  116. Robinett, C.C., O’Connor, A. and Dunaway, M. (1997). The repeat organizer, a specialized insulator element within the intergenic spacer of the Xenopus rRNA genes. Mol Cell Biol 17(5), 2866−2875
  117. Rollins R.A., Morcillo P. and Dorsett D. (1999). Homologue of chromosomal adherins, participates in activation by remote enhancers in the cut and Ultrabithorax genes. Genetics, v.152, 577−593
  118. Ruppert J., Kinzler K., Wong A., Bigner S., Kao F., Law M., Seuanez H., O’Brien S., Vogelstein B. (1988). The GLI-Kruppel family of human genes. Mol Cell Biol., 8,3104−3113
  119. Safak M., Gallia, G.L., Ansari, S.A. and Khalili, K. (1999) Physical and functional interaction between the Y-box binding protein YB-1 and human polyomavirus JC virus large T antigen. J. Virol., 73, 10 146−10 157
  120. Saitoh, N., Bell, A.C., Reeillas-Targa, F" West, A.G., Simpson, M., Pikaart, M., Felsenfeld, G. (2000) «Structural and functional conservation at the boundaries of the chicken fi-globin domain». EMBO J. 19: 2315 2322
  121. Sambrook P.N., Eisman J.A., Champion G.D., Cohen M.L., Pocock N.A. and Yeates M.G. (1989) Effect of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study. Ann Rheum Dis. 48: 535−538
  122. G.L. (1994). Transcriptional regulation of gene exptession: mechanism and pathophysiology. Human Mutation 3: 180−199
  123. Szabo, P.E., Pfeifer, G.P., Mann, J.R. (2004) «Parent-of-origin-specific binding of nuclear hormone receptor complexes in the H19-Igf2 imprinting control region». Mol Cell Biol.- 24(11):4858−68
  124. Szabo P., Tang S., Silva F., Tsark W., and Mann J. (2004). Role of CTCF Binding Sites in the Igf2/H19 Imprinting Control Region, MOLECULAR AND CELLULAR BIOLOGY, Vol. 24, № 11, 4791−4800.
  125. Takai, D., Gonzales, F.A., Tsai, Y.C. Thayer, M.J., Jones, P.A. (2001) «Large scale mapping of methylcytosines in CTCF-binding sites in the human H19 promoter and aberrant hypomethylation in human bladder cancer». Hum Mol Genet.- 10(23):2619−26
  126. O., Rudt F., Guddat U., Mentzel H., Pieler T. (1992). RNA and DNA binding zing fingers in Xenopus TFIIIA. Cell, 71, 679−690
  127. , S.M. (1999) «The sins of the fathers and mothers: genomic imprinting in mammalian development». Cell. Jan 22- 96(2): 185−93
  128. Tolhuis, Π’., Palstra, R. J, Splinter, E., Grosveld, F., and de Laat, W. 2002. Looping and interaction between hypersensitive sites in the active P-globin locus. Mol. Cell 10: 1453−1465
  129. Torrano V, Chernukhin I., Docquier F., D’Arcy V, Leon J., Klenova E., Dolgado M. D (2005). CTCF regulates groth and erythroid differentiation of human myeloid leukemia cells. J. Biol. Chem. 280: 28 152−28 161.
  130. Y.P., Huang S.J., Chang J.L. (1999). Adenovirus mediated p21(WAFl/SDII/CIPl) gene transfer induces apoptosis of human cervical cancer cell lines. J. Virol, 73,4983−4990
  131. Tybulewicz, V. L, Crawford, C. E, Jackson, P. K, Bronson, R.T. and Mulligan, R.C. (1991). Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 65(7), 1153−1163
  132. Yang, X.J., Ogryzko, V. V, Nishikawa, J, Howard, B. H, Nakatani, Y. (1996). «A Ρ€Π—ΠžΠž/CBP-associated factor that competes with the adenoviral oncoprotein El A.» Nature. 382(6589): 319−24.
  133. Yusufzai Π’., Tagami H, Nakatani Y, and Felsenfeld G. (2004). CTCF Tethers an Insulator to Subnuclear Sites, Suggesting Shared Insulator Mechanisms across Species. Molecular Cell, Vol. 13, 291−298.
  134. Valadez-Graham V, Razin S. V, Recillas-Targa (2004). CTCF-dependent enhancer blockers at the upstream region of the chicken a-globin gene domain. Nucleic Acids Res. vol.32 (4) 1354−1362
  135. Vostrov A.A. and Quitschke W. W (1997). The zinc finger protein CTCF binds to the APB-P domain of the amyloid precursor protein promoter. J. Biol. Chem., 272, 33 353−33 359
  136. Vostrov, A.A., Taheny, M.J., Quitschke, W.W. (2002). «A Region to the N-terminal Side of the CTCF Zinc Finger Domain Is Essential for Activating Transcription from the Amyloid Precursor Protein Promoter.» J. Biol. Chem. 277: 1619−1627
  137. Wei G., Liu P., Liang C.(2005). Chromatin domain boundaries: insulator and beyond. Cell Research, 15(4), 292−300
  138. Wenqiang, Π’., Yi, G., Yu, S., Jung, Π’., DaYe, S. (1997) «Extracellular calmodulin-binding proteins in body fluids of animals». J Endocrinol. Oct- 155(l):13−7
  139. West, A.G., Gaszner, M., Felsenfeld, G. (2002). «Insulators: many functions, many mechanisms.» Genes Dev. 16: 271−288.
  140. West A. and Fraser P. (2005). Remote control of gene transcription. Hum.Mol.Genet., 14, R101−110
  141. D.A., Vilalta A., Oshima R.G. (2000). An Alu element from the K18 gene confers position-independent expression in trasgenic mice. J. Biol.Chem. v. 275 (2):759−768
  142. Wingender E., Dietze P., Karas H., Knuppel R.(1996). TRANSFAC: a database on transcription factors and their DNA binding sites. Nucleic Acids Res., 24(1):238−41
  143. Ru Zhang, Les J. Burke, John E.J. Rasko, Victor Lobanenkov, Rainer Renkawitza (2004). Dynamic association of the mammalian insulator protein CTCF with centrosomes and the midbody. Experimental Cell Research 294: 86−93
  144. Zhan H. C., Liu, D.P. et al. (2001). «Insulator: from chromatin domain boundary to gene regulation.» Hum Genet 109(5): 471−478
  145. Zhao, H. and Dean A. (2004). An insulator blocks spreading of histone acetylation and interferes with RNA polymerase II transfer between an enhancer and gene. Nucleic Acids Res. 32,4903−4919
  146. Zhong, X.P. and Krangel, M.S. (1997). An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus. PNAS USA 94(10), 5219−5224
Π—Π°ΠΏΠΎΠ»Π½ΠΈΡ‚ΡŒ Ρ„ΠΎΡ€ΠΌΡƒ Ρ‚Π΅ΠΊΡƒΡ‰Π΅ΠΉ Ρ€Π°Π±ΠΎΡ‚ΠΎΠΉ