Chromatin features and the epigenetic regulation of pluripotency states in ESCs

Abstract

In pluripotent stem cells, the interplay between signaling cues, epigenetic regulators and transcription factors orchestrates developmental potency. Flexibility in gene expression control is imparted by molecular changes to the nucleosomes, the building block of chromatin. Here, we review the current understanding of the role of chromatin as a plastic and integrative platform to direct gene expression changes in pluripotent stem cells, giving rise to distinct pluripotent states. We will further explore the concept of epigenetic asymmetry, focusing primarily on histone stoichiometry and their associated modifications, that is apparent at both the nucleosome and chromosome-wide levels, and discuss the emerging importance of these asymmetric chromatin configurations in diversifying epigenetic states and their implications for cell fate control.

The Chd1 chromatin remodeler shifts hexasomes unidirectionally

“…A fundamental characteristic of the histone code is the combinatorial diversity achieved from multiple marks, which may or may not reside on the same histone tail (Ruthenburg et al, 2007; Tee and Reinberg, 2014). Both through post-translational modifications (PTMs) and substitution of histone variants, additional chemical diversity arises from asymmetric modifications of nucleosomes.…”

Cell totipotency: molecular features, induction, and maintenance

“…ESCs can contribute to different embryonic lineages when injected into pre-implantation embryos or differentiated in vitro [12]. Since ESCs are capable of self-renewal in culture and have great potential in regenerative medicine, the transcriptional and epigenetic networks regulating their pluripotency have been extensively studied [13-15]. The knowledge gained from these studies not only contributed to the optimization of culturing conditions for maintaining ESC pluripotency, but also led to the discovery of induced pluripotent stem cell (iPSC) through manipulating transcriptional and epigenetic networks [16, 17].…”

Procollagen Lysyl Hydroxylase 2 Expression Is Regulated by an Alternative Downstream Transforming Growth Factor β-1 Activation Mechanism

“…Both types of chemical modifications are able to affect the compaction of chromatin either directly via charge differences of the histone tails that are connected to the DNA, or indirect by attracting chromatin remodeling complexes. These changes in chromatin compaction are thought to interfere with transcriptional activity by affecting the accessibility of transcription factors and transcription initiation complexes or even elongation of RNA polymerase II complexes (27)(28)(29)(30). The acetylation status of histones are balanced by histone acetyltransferases (HATs) that add acetyl groups and are related to gene activation, whereas histone deacetylases (HDACs) that cleave acetyl groups (31,32) are related to gene repression.…”