HISTONE MODIFICATIONS ON PROMOTERS OF HUMAN <i>Oct4 </i>AND <i>Nanog </i>GENES AT ONSET OF NEURAL DIFFERENTIATION OF NT2/D1 CELLS
Transcription factors OCT4 and NANOG are the main constituents of the functional network that controls proliferation and pluripotency maintenance of stem cells as well as early lineage decisions. We investigated expression profiles of OCT4 and NANOG during the early phases of neural differentiation using NT2/D1 cells induced by RA as an in vitro model system of human neurogenesis. We demonstrated decrease in OCT4 and NANOG mRNA and protein levels following exposure to RA. Next, by employing ChIP, we investigated profiles of selected H3 and H2B histone marks deposited on the promoters of the OCT4 and NANOG genes. We found decline in H3K4me3, H2BK5ac, and H2BK120ac on both promoters, which paralleled the decrease in OCT4 and NANOG expression. Moreover, we found that the H2BK16ac mark is differentially enriched on these two promoters, pointing to differences in epigenetic regulation of the expression of the OCT4 and NANOG genes. Finally, based on our data, we suggest that the early response of pluripotency genes OCT4 and NANOG to differentiation-inducing stimuli is mediated by dynamic changes in chromatin marks, while DNA methylation is acquired in the later stages of neurogenesis.