Transient Polycomb activity represses developmental genes in growing oocytes

作者：Ellen G. Jarred, Zhipeng Qu, Te‐Sha Tsai, Ruby Oberin, Sigrid Petautschnig, Heidi Bildsoe, Stephen Pederson, Qing-Hua Zhang, Jessica M. Stringer, John Carroll, David K. Gardner, Maarten van den Buuse, Natalie A. Sims, William T. Gibson, David L. Adelson, Patrick Western · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2022 · DOI：10.1101/2022.09.18.508436 · 被引用次数：1 · 研究领域：Epigenetics and DNA Methylation、Genetic Syndromes and Imprinting、Prenatal Screening and Diagnostics

Abstract Background Non-genetic disease inheritance and offspring phenotype is substantially influenced by germline epigenetic programming, including genomic imprinting. Loss of Polycomb Repressive Complex 2 (PRC2) function in oocytes causes non-genetically inherited effects on offspring, including embryonic growth restriction followed by post-natal offspring overgrowth. While PRC2 dependent non-canonical imprinting is likely to contribute, less is known about germline epigenetic programming of non-imprinted genes during oocyte growth. In addition, de novo germline mutations in genes encoding PRC2 lead to overgrowth syndromes in human patients, but the extent to which PRC2 activity is conserved in human oocytes is poorly understood. Results In this study we identify a discrete period of early oocyte growth during which PRC2 is expressed in mouse growing oocytes. Deletion of Eed during this window led to the de-repression of 343 genes. A high proportion of these were developmental regulators, and the vast majority were not imprinted genes. Many of the de-repressed genes were also marked by the PRC2-dependent epigenetic modification histone 3 lysine 27 trimethylation (H3K27me3) in primary-secondary mouse oocytes, at a time concurrent with PRC2 expression. In addition, we found H3K27me3 was also enriched on many of these genes by the germinal vesicle (GV) stage in human oocytes, strongly indicating that this PRC2 function is conserved in the human germline. However, while the 34...