Distinct Epigenomic Landscapes of Pluripotent and Lineage-Committed Human Cells

Abstract

SUMMARY Human embryonic stem cells (hESCs) share an identical genome with lineage-committed cells, yet possess the remarkable properties of self-renewal and pluripotency. The diverse cellular properties in different cells have been attributed to their distinct epigenomes, but how much epigenomes differ remains unclear. Here, we report that epigenomic landscapes in hESC and lineage committed cells are drastically different. By comparing the chromatin modification profiles and DNA methylomes in hESCs and primary fibroblasts, we find that nearly one-third of the genome differs in chromatin structure. Most changes arise from dramatic redistributions of repressive H3K9me3 and H3K27me3 marks, which form blocks that significantly expand in fibroblasts. A large number of potential regulatory sequences also exhibit a high degree of dynamics in chromatin modifications and DNA methylation. Additionally, we observe novel, context-dependent relationships between DNA methylation and chromatin modifications. Our results provide new insights into epigenetic mechanisms underlying properties of pluripotency and cell-fate commitment.

Physiological regulation of transgene expression by a lentiviral vector containing the A2UCOE linked to a myeloid promoter

“…Nevertheless, these observations imply that A2UCOE simply supports the inherent epigenetic state and transcriptional activity of cellular promoters in P19 cells. This view is consistent with the fact that the MRP8 promoter in our vectors adopts the epigenetic state of its endogenous counterpart in ES cells (Supplementary Figure 3 and Harris et al 29 ; Hawkins et al 30 ; Wang et al 31 ). Accordingly, the A2UCOE chromatin remodeling activity does not interfere with the inherently encoded epigenetic state and transcriptional regulation of linked promoters, but prevents or reduces the influence of the chromosomal environment.…”

NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells

“…Reprogramming of somatic cells into pluripotent stem cells requires changes in chromatin structure that mediate silencing of lineage-specific genes and activation of pluripotency genes [27,28]. Chromatin remodelers play active, regulatory roles during the reprogramming process, facilitating binding of transcription activators to regulatory gene sequences and upregulation of reprogramming factors [29].…”

Concise Review: Induced Pluripotent Stem Cells Versus Embryonic Stem Cells: Close Enough or Yet Too Far Apart?

“…Another comparative analysis was done on histone three lysine methylation by CHIP-Seq, with an improved computational method to detect not only peaks, but also long stretches of these marks [62]. This analysis highlighted the difference between human fibroblasts and pluripotent cells by showing that fibroblasts have more repressive chromatin due to the [24,27,28].…”