Abstract：
:Adult germline stem cells (AGSCs) self-renew (Thy1(+) enriched) or commit to gametogenesis (Kit(+) enriched). To better understand how chromatin regulates AGSC biology and gametogenesis, we derived stage-specific high-resolution profiles of DNA methylation, 5hmC, histone modifications/variants, and RNA-seq in AGSCs and during spermatogenesis. First, we define striking signaling and transcriptional differences between AGSC types, involving key self-renewal and proliferation pathways. Second, key pluripotency factors (e.g., Nanog) are silent in AGSCs and bear particular chromatin/DNAme attributes that may "poise" them for reactivation after fertilization. Third, AGSCs display chromatin "poising/bivalency" of enhancers and promoters for embryonic transcription factors. Remarkably, gametogenesis occurs without significant changes in DNAme and instead involves transcription of DNA-methylated promoters bearing high RNAPol2, H3K9ac, H3K4me3, low CG content, and (often) 5hmC. Furthermore, key findings were confirmed in human sperm. Here, we reveal AGSC signaling asymmetries and chromatin/DNAme strategies in AGSCs to poise key transcription factors and to activate DNA-methylated promoters during gametogenesis.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Hammoud SS,Low DH,Yi C,Carrell DT,Guccione E,Cairns BRdoi
10.1016/j.stem.2014.04.006subject
Has Abstractpub_date
2014-08-07 00:00:00pages
239-53issue
2eissn
1934-5909issn
1875-9777pii
S1934-5909(14)00143-Xjournal_volume
15pub_type
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