Regulation of Large-Scale Chromatin Structure and Epigenetic Control of Gene Expression during Oogenesis
Chromatin configuration in the nucleus or germinal vesicle (GV) of mammalian oocytes undergoes dynamic epigenetic modifications during oocyte growth. A crucial developmental transition at the culmination of oogenesis, large-scale chromatin remodeling in the GV is essential to confer the female gamete with meiotic and developmental potential. Using several models for the experimental manipulation of chromatin structure and function in combination with cell and molecular biology approaches, our current work seeks to determine the cellular pathways and factors that are involved in remodeling chromatin in the mammalian oocyte genome.
Role of Chromatin Modifications during Meiosis
Centromeric heterochromatin formation is essential for chromosome architecture, transcriptional silencing and chromosome segregation.
However, little is known concerning the epigenetic control of heterochromatin formation in the mammalian germ line. Using RNA interference (RNAi) we have begun to explore the role of ATRX, a heterochromatin binding protein with chromatin remodeling activity, during meiosis. ATRX is present at centromeric domains in the germinal vesicle of mouse oocytes and becomes exclusively associated with centromeres of chromosomes at metaphase I or metaphase II of meiosis, where it is required to mediate chromosome-microtubule interactions in the female gamete. Moreover, we currently study the role of the lymphocyte-specific helicase (LSH) on meiotic chromosome synapsis, heterochromatin formation and maintenance of genomic stability in the female germ line.
KEY WORDS: Meiosis, chromatin remodeling, centromeric heterochromatin, epigenetic modifications, ATRX, LSH, PARP-1, CBX2