Dual Roles of Histone H3 Lysine 9 Acetylation in XXXX Embryonic Stem Cell Pluripotency and Neural Differentiation.

@entity1 @entity71728 @entity3997 @entity3493 @entity245 @entity376
UNASSIGNED: Early neurodevelopment requires cell fate commitment from pluripotent stem cells to restricted neural lineages, which involves the epigenetic regulation of chromatin structure and lineage-specific gene transcription. However, it remains unclear how histone H3 @entity376 9 acetylation (H3K9Ac), an epigenetic mark representing transcriptionally active chromatin, is involved in the neural commitment from pluripotent embryonic stem cell (ESC). In this study, we demonstrate that H3K9Ac gradually declines during the first 4 days of in vitro neural differentiation of @entity1 ESCs (hESCs) and then increases during day 4-8. Consistent with this finding, the H3K9Ac enrichment at several pluripotency genes was decreased, and H3K9Ac occupancies at the loci of neurodevelopmental genes increased during hESC neural commitment. Inhibiting H3K9 deacetylation on days 0-4 by histone deacetylase inhibitors (HDACis) promoted hESC pluripotency and suppressed its neural differentiation. Conversely, HDACi-elicited upregulation of H3K9 acetylation on days 4-8 enhanced neural differentiation and activated multiple neurodevelopmental genes. Mechanistically, HDACis promote pluripotency gene transcription to support hESC self-renewal through suppressing @entity3997 activity. During hESC neural commitment, HDACis relieve the inhibitory activities of @entity71728 and thereby promote early neurodevelopmental gene expression by interfering with gene-specific histone acetylation patterns. Furthermore, @entity3493 is primarily identified as the major histone acetylation factors involved in both hESC pluripotency and neural differentiation. Our results indicate that epigenetic modification plays pivotal roles during the early neural specification of hESCs. The histone acetylation, which is regulated by distinct HDAC members at different @entity245 , plays dual roles in hESC pluripotency maintenance and neural differentiation.
