Epigenetic Transfiguration of H3K4me2 to H3K4me3 During Differentiation of Embryonic Stem Cell into Non-embryonic Cells

摘要

Chromatin immune precipitation followed by high-throughput sequencing (Chip-Seq), investigate the genome-wide distribution of all histone modifications. Lysine residues within histones di or tri-methylated in Saccharomyces cerevisiae have been studied earlier. Tri-methylation of Lys 4 of histone H3K4me3 correlates with transcriptional activity, but little is known about this methylation state in human. It was also previously proved that deposition of H3K4me2 modification at TSS is associated with gene repression in the yeast cell. Overlapping non-coding RNA (ncRNA) transcript assumes a crucial role in this repression. Here, we examine the H3K4me2 and H3K4me3 methylation dynamics at the TSS region of human genes across the ENCODE (https://www. encode project. org/) Consortium 8 cell lines GM12878, H1-hESC, HeLa-S3, HepG2, HSMM, HUVEC, K562 and NHEK, we identified clear divergence of histone modification profiles in H1-hESC with respect to others. While, H3K4me2 modifications were found to be associated with the vast majority of genes in the H1-hESC with a significantly decreased amount in other differentiated cell lines, H3K4me3 modification showed completely reverse trends. By the process of differentiation, a distinct set of genes lose H3K4me2 in H1-hESCand gain H3K4me3 in differentiated cell, thereby, enhancing the expression level of the corresponding genes. On the level of gene ontology molecular function classification, these genes are mostly associated with protein binding, nucleotide binding, DNA binding and ATP binding. Other than that, signaling and receptor activity, metal ion binding and phosphorylation-dephosphorylating action can be correlated with these genes. We expect a crosstalk between the change of methylation status and gene functionality, as all these functions can be allied to transcriptional regulation and gene activation, which once again is linked to H3K4me3 mark.