Chromatin remodelling during development

Abstract

New methods for the genome-wide analysis of chromatin are providing insight into its roles in development and their underlying mechanisms. Current studies indicate that chromatin is dynamic, with its structure and its histone modifications undergoing global changes during transitions in development and in response to extracellular cues. In addition to DNA methylation and histone modification, ATP-dependent enzymes that remodel chromatin are important controllers of chromatin structure and assembly, and are major contributors to the dynamic nature of chromatin. Evidence is emerging that these chromatin-remodelling enzymes have instructive and programmatic roles during development. Particularly intriguing are the findings that specialized assemblies of ATP-dependent remodellers are essential for establishing and maintaining pluripotent and multipotent states in cells.An essential aspect of building a mammalian cell is packing 1.7 metres of DNA into a 5-micrometre nucleus in a form that allows it to be replicated and transcribed in stable, tissuespecific patterns. The basic unit of chromatin assembly is the nucleosome 1 , which compacts DNA about sevenfold. However, because the overall level of compaction of the vertebrate genome is several thousand fold, relatively little of the DNA in vertebrates is present on simple nucleosomal templates in vivo. Instead, most chromatin is present in undefined, highly compacted structures that remain available for the induction of developmental programs that specify cell fate and morphogenesis.At least three processes control the assembly and regulation of chromatin: DNA methylation (see ref. 2 for a review); histone modifications (see ref. 3 for a review); and ATP-dependent chromatin remodelling, which is the focus of this Review. ATP-dependent remodelling seems to be crucial for both the assembly of chromatin structures and their dissolution. About 30 genes encode the ATPase subunits of these complexes in mammals. With few exceptions, these ATPases seem to be genetically non-redundant, with mutation of the encoding genes often having severe effects on the early embryo or giving rise to maternaleffect phenotypes (in which the phenotype of the embryo reflects the genotype of the mother). Indeed, in many cases, the genes encoding the ATPases or their subunits are haploinsufficient (that is, one copy is insufficient for development), indicating that their role in specific processes is rate limiting. Despite their genetic non-redundancy, the various ATPases seem to have similar activities when studied in vitro: they all increase nucleosome mobility 4 . Therefore, it is clear that better in vitro assays are needed to tease apart their biological functions.Correspondence should be addressed to G.R.C. (crabtree@stanford.edu). Author Information Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests. NIH Public Access Author ManuscriptNature. Author manuscript; available in PMC 2011 March 18. NIH-PA Au...

Epigenetic regulation of aging stem cells

“…However, we also note that regulators of DNA methylation are required for the function of a variety of adult stem cells (Zhao et al, 2003;Ma et al, 2009;Trowbridge et al, 2009;Sen et al, 2010;Trowbridge and Orkin, 2010;Wu et al, 2010), and that they complex with chromatin modifiers to elicit changes in chromatin state (Jones et al, 1998;Nan et al, 1998;Fuks et al, 2003). In addition, chromatin remodeling factors are also important for stem and progenitor cell function (Lessard et al, 2007;Ho et al, 2009;Ho and Crabtree, 2010), suggesting that several epigenetic mechanisms could coordinately control adult stem cell gene expression programs during organismal aging.…”

Use of chromatin remodeling ATPases as RNAi targets for parental control of western corn rootworm (Diabrotica virgifera virgifera) and Neotropical brown stink bug (Euschistus heros)

“…Brahma-related proteins and SNF2-type chromatin-remodeling ATPases are subunits of chromatin remodeling complexes that play global roles in mobilizing nucleosomes. These proteins stably change chromatin accessibility and alter gene expression during critical stages of development (Bouazoune and Brehm, 2006;Ho and Crabtree, 2010). Thus, a short-term RNAi exposure that targets a chromatin-remodeling ATPase can potentially lead to long-lasting effects.…”

“…Gene activation and silencing during this period is largely accomplished through epigenetic modifications of chromatin that involve DNA methylation, histone modification, and the function of ATP-dependent remodeling complexes (de la Serna et al, 2006;Ho and Crabtree, 2010). The ATP-dependent remodeling enzymes are a class of ATPases that contain a SNF2 domain (sucrose non-fermenting, originally identified in Saccharomyces cerevisiae) (Durr et al, 2005;Eisen et al, 1995).…”

“…Consequently, most of the chromatin-remodeling ATPases are essential for an organism's viability and development. More specifically, chromatin remodelers are needed for activation of specific genes such as homeotic genes that regulate body segmentation during development and may be necessary during gametogenesis (for review, see e.g., Ho and Crabtree (2010)). The ATP-dependent remodeling enzymes are generally divided into families based on functional domains that facilitate histone interactions (e.g., bromodomain, chromodomain, and SANT).…”

Senomic view of the cell: Senome versus Genome

“…Epigenomics encompasses chemical modifications of DNA such as methylation, histones, chromatin-remodeling protein complexes [61], and other nuclear proteins, chaperones and some aspects of the dynamic cytoplasmic cytoskeleton [62]. All of these are deeply interlinked with the endocytic matrix [63] that integrates the Senome with the epigenome and genome [63].…”