期刊
GENES & DEVELOPMENT
卷 29, 期 23, 页码 2449-2462出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.271353.115
关键词
oocytes; DNA methylation; genomic imprinting; histone modifications; ChIP-seq
资金
- Medical Research Council of the UK
- Rising Star Award from the Cancer Prevention and Research Institute of Texas (CPRIT) [R1108]
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7 under Research Executive Agency [290123]
- BBSRC [BBS/E/B/000C0403, BBS/E/B/000C0400] Funding Source: UKRI
- MRC [MR/K011332/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0403, BBS/E/B/000C0400, 1129285] Funding Source: researchfish
- Medical Research Council [MR/K011332/1] Funding Source: researchfish
Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.
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