High‐wire act: the poised genome and cellular memory

Abstract

Emerging evidence aided by genome‐wide analysis of chromatin and transcriptional states has shed light on the mechanisms by which stem cells achieve cellular memory. The epigenetic and transcriptional plasticity governing stem cell behavior is highlighted by the identification of ‘poised’ genes, which permit cells to maintain readiness to undertake alternate developmental fates. This review focuses on two crucial mechanisms of gene poising: bivalent chromatin marks and RNA polymerase II stalling. We provide the context for these mechanisms by exploring the current consensus on the regulation of chromatin states, especially in quiescent adult stem cells, where poised genes are critical for recapitulating developmental choices, leading to regenerative function.

Apolipoprotein E region molecular signatures of Alzheimer's disease

“…Ten functional variants were found to exist in active expression states in multiple cell lines, ranging from 1 (rs387976) to 63 (rs157580 [ TOMM40 ]) of 68 cell types with data available from Ensembl. All of these variants can be in a poised state in one or more cell types (i.e., they can be epigenetically activated at a later stage in development or in response to exogenous stimuli) (Creyghton et al., 2010; Murao, Noguchi & Nakashima, 2016; Puri, Gala, Mishra & Dhawan, 2015). Two variants, rs1871046 ( NECTIN2 ) and rs440446 ( APOE ), were characterized as being a poised expression state in many cell types (20 and 32 epigenomes, respectively).…”

“…Recent data indicate that the function of astrocytes can change from potent pro‐inflammatory to potent anti‐inflammatory in response to regulatory signals (Sofroniew, 2015). Genes in poised expression states in relevant cell types can be activated by changes in the epigenome later in development or by environmental cues (Creyghton et al., 2010; Murao et al., 2016; Puri et al., 2015). These observations strongly suggest that AD development could be the result of a complex transcriptional regulatory structure modulating regional gene expression (Fitzsimons et al., 2014) supported by clustering of alleles in the molecular signatures identified in the APOE region.…”

Low-Cell-Number Epigenome Profiling Aids the Study of Lens Aging and Hematopoiesis

“…For example, in multi-potential hematopoietic cells such as the established EML cell line, hematopoietic-specific genes may be poised by H3K4me2-positive and H3K4me3-negative marks (Orford et al, 2008). RNA polymerase II pausing on promoters may also poise genes for expression (Puri et al, 2015). The FARP-ChIP-seq strategy reported here should aid in the further study of how HSCs poise genes for lineage differentiation.…”

Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway

“…In stem cells, genes implicated in lineage determination and progression are found in a poised state: although transcriptionally silent, they contain active histone marks that keep them prepared to be expressed after receiving differentiation signals (Puri et al, 2015; Rumman et al, 2015). In quiescent satellite cells, chromatin is kept in a transcriptionally permissive state, with many genes harboring the activation H3K4me3 mark at the transcription start sites (TSS), including MyoD and Myf5, and a few number of genes labeled with the inhibitory H3K27me3 mark (Liu et al, 2013).…”