Chromatin Modifications During Mammalian Oocyte Growth and Meiotic Maturation

The mammalian oocyte nucleus or germinal vesicle (GV) exhibits a unique chromatin configuration regulated by dynamic histone modifications and striking large-scale chromatin remodeling. Functional differentiation of chromatin structure during mammalian oocyte growth is essential for the acquisition of both meiotic and developmental potential. Chromatin modifications acquired during a critical window of postnatal oocyte growth are essential to regulate gene expression as well as the establishment of maternal-specific DNA methylation marks or genomic imprinting. De novo methylation begins around the time when the oocyte reaches a 50 μM diameter in preantral follicles and is completed before global transcriptional repression takes place in fully-grown preovulatory oocytes at the germinal vesicle stage. Establishment of DNA methylation occurs on a locus-by-locus basis and both histone modifications and transcription at regulatory sequences dictate the placing and timing of methylation marks at specific genes. Changes in transcription may thus coordinate the progressive establishment of maternal methylation marks with oocyte growth. Importantly, compelling evidence indicates that establishment of the correct epigenetic landscape during oogenesis as well as large-scale chromatin remodeling are indispensable for pericentric heterochromatin formation, meiotic centromere function and accurate chromosome segregation. Functional differentiation of chromatin structure is regulated by multiple and hierarchical epigenetic modifications established at critical developmental transitions by chromatin remodeling proteins and histone post-translational modifications. Understanding the basic mechanisms of epigenetic maturation of the mammalian oocyte and the emerging links between chromatin remodeling and transcription will be essential to determine the effects of environmental and hormonal changes induced by exposure to endocrine disruptors, changes in maternal nutritional status or assisted reproductive technologies and their impact on the oocyte transcriptional profile, establishment of maternal DNA methylation and maintenance of chromosome stability during oogenesis.