Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells

Abstract

We mapped Polycomb-associated H3K27 trimethylation (H3K27me3) and Trithorax-associated H3K4 trimethylation (H3K4me3) across the whole genome in human embryonic stem (ES) cells. The vast majority of H3K27me3 colocalized on genes modified with H3K4me3. These commodified genes displayed low expression levels and were enriched in developmental function. Another significant set of genes lacked both modifications and was also expressed at low levels in ES cells but was enriched for gene function in physiological responses rather than development. Commodified genes could change expression levels rapidly during differentiation, but so could a substantial number of genes in other modification categories. SOX2, POU5F1, and NANOG, pluripotency-associated genes, shifted from modification by H3K4me3 alone to colocalization of both modifications as they were repressed during differentiation. Our results demonstrate that H3K27me3 modifications change during early differentiation, both relieving existing repressive domains and imparting new ones, and that colocalization with H3K4me3 is not restricted to pluripotent cells.

Histone H3K27me3 demethylases KDM6A and KDM6B modulate definitive endoderm differentiation from human ESCs by regulating WNT signaling pathway

“…We found that WNT agonists, but not BMP or FGF agonists, partially rescued the endoderm differentiation defect phenotype ( Figure 2A), indicating that the WNT pathway might be relevant. Consistent with this notion, analysis of previous ChIPseq results [16,17] of H3K27me3-enriched genes in human ESCs revealed that the WNT signaling pathway is highly enriched for H3K27me3 (Supplementary information, Figure S5, P = 0.00007), making genes of the WNT pathway likely relevant targets for KDM6A or KDM6B regulation. Consequently, we focused our attention on the WNT pathway.…”

“…Quantitative PCR was carried out as above. The primers were designed according to the published H3K27me3 ChIP-seq data [16,17] and listed in Supplementary information, Table S2.…”

Smad2 mediates Activin/Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells

“…Specific state of histone modification plays crucial roles in ES cell fate determination, and the genes harboring both histone H3K4 trimethylation (me3) and H3K27me3 modification -so called "bivalent" genes -are regarded to largely encode important developmental regulators in ES cells [29][30][31]. Thus, we examined the status of bivalent and other related modifications of our Smad2-associated genes by comparing with previously reported histone modification data of ES cells [32].…”

KMT1E Mediated H3K9 Methylation Is Required for the Maintenance of Embryonic Stem Cells by Repressing Trophectoderm Differentiation

“…Histone methylation at distinct lysines in the tails of the core histones H3 and H4 plays a paramount role in regulating gene transcription (reviewed in [9]), and the status of histone methylation in mouse and human ES cells has been mapped extensively on a genomewide scale [10][11][12][13][14]. In particular, histone H3 lysine 4 and lysine 27 trimethylation (H3K4me3 and H3K27me3, respectively) were demonstrated to be of importance.…”