Идентификация и картирование участков ДНК, специфически связывающихся с ядерным матриксом, на хромосоме 19 человека тема автореферата и диссертации по химии, 02.00.10 ВАК РФ

СПИСОК СОКРАЩЕНИЙ

ВВЕДЕНИЕ 6 ОБЗОР ЛИТЕРАТУРЫ. Доменная организация генетического материала в клеточном ядре.

I. Упаковка генетического материала в клеточном ядре

II. Остаточные структуры интерфазного ядра и их биохимический состав

П. 1. Белки остаточной ядерной оболочки

11.2. Белки остаточного ядрышка

11.3. Белки внутреннего ядерного матрикса 14 II. 4. Минорные белки

II.5. Другие компоненты ядерного матрикса

III. ДНК в составе ядерного матрикса, ее свойства и функции

III. 1. Определение и способы получения ДНК ядерного матрикса 18 III.2. Структурные особенности ДНК ядерного матрикса 20 III. 3. Функции ДНК ядерного матрикса

111.3.1. Петельные домены

111.3.2. Тканеспецифичность доменов

111.3.3. Нейтрализация эффекта положения

111.3.4. S/MARs как участки интеграции ретровирусных векторов

111.3.5. S/MARs в составе ретроэлементов

IV. Белки специфически связывающиеся с S/MAR-элементами

V. Доменная структура хроматина в геномном контексте

V. 1. S/MARs и петлевые домены

V.2. S/MARs и геномные последовательности

V.3. Интронные S/MARs

V.4. S/MARs и другие регуляторные элементы генома

Основные результаты и выводы

1. Методом селекции геномных последовательностей, предпочтительно связывающихся с ядерным матриксом, получены и картированы на хромосоме 19 человека 28 новых S/MAR-элементов.

2. Идентифицирован и картирован на хромосоме 19 человека повторяющийся S/MAR-элемент, связанный с семейством генов канцероэмбриональных антигенов (CEA-MAR). Высказано предположение о том, что дупликация генов семейства может происходить по границам петлевых доменов хроматина.

3. Реконструирована доменная структура локуса хромосомы 19 человека длиной 1 млн.п.о., расположенного между маркерами D19S208 и СОХ7А1. S/MAR-элементы подразделяют локус на 10 доменов длиной от 6 до 272 т.п.о. Средний размер домена составляет 88 т.п.о.

4. Семь S/MAR-элементов находятся в интронах генов MAG, APLP1, HSPOX1, NPHS1, CACNA1A и PIN1. Эти гены, кроме PIN 1, экспрессируются тканеспецифично и связаны с наследственными заболеваниями. Такое расположение S/MARs позволяет предположить их участие в регуляции экспрессии данных генов.

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