Maternal depletion of CTCF reveals multiple functions in transcription and development / Le-Ben Wan.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Wan, Le-Ben.

Contributor:

Bartolomei, Marisa S., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Cell and Molecular Biology.

Academic Dissertations as Topic.

Medical Subjects:

Cell and Molecular Biology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Physical Description:

xi, 181 pages : color illustrations ; 29 cm

Production:

2008.

Summary:

CTCF is a multifunctional nuclear factor involved in epigenetic regulation. Despite recent advances that include the systematic discovery of CTCF binding sites throughout the mammalian genome, the in-vivo roles of CTCF in adult tissues and during development are largely unknown. Using transgenic RNAi, we previously depleted maternal stores of CTCF from growing mouse oocytes. In this dissertation, I detail a global and essential role for CTCF in transcription and preimplantation embryo development. Using expression microarrays, we find that CTCF predominantly activates or derepresses hundreds of genes in oocytes. This finding supports an increasingly evident view that insulators function through active transcription rather than through passive tethering. CTCF depletion causes meiotic defects in the egg, and mitotic defects in the embryo that are accompanied by defects in zygotic gene expression, and culminate in apoptosis. Maternal pronuclear transfer and Ctcf mRNA microinjection experiments indicate that CTCF is a mammalian maternal effect gene, one of a small few that have been identified in mammals. These experiments also indicate that persistent defects in maternally loaded factors rather than persistent chromatin defects perturb early embryonic development. Overall, our findings suggest that the inherent function of CTCF is to regulate transcription rather than chromatin structure.

Notes:

Adviser: Marisa S. Bartolomei.

Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 2008.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3346212