Chromatin remodelling: the industrial revolution of DNA around histones

Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R.

doi:10.1038/nrm1945

Cited by 511 publications

(452 citation statements)

References 127 publications

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“…3c, arrow). This creates a small DNA loop near the dyad, which can then propagate around the distal part of nucleosome by one-dimensional diffusion 9,41 (not depicted). The internal translocase has been proposed to function as an internal DNA ratchet as well as a DNA pump, enforcing the movement of DNA in one direction, toward the dyad 41 .…”

Section: Remodelers Can Translocate Dna From a Fixed Internal Sitementioning

confidence: 99%

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Chromatin remodeling: insights and intrigue from single-molecule studies

Cairns

2007

Nat Struct Mol Biol

227

208

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Chromatin remodelers are ATP-hydrolyzing machines specialized to restructure, mobilize or eject nucleosomes, allowing regulated exposure of DNA in chromatin. Recently, remodelers have been analyzed using single-molecule techniques in real time, revealing them to be complex DNA-pumping machines. The results both support and challenge aspects of current models of remodeling, supporting the idea that the remodeler translocates or pumps DNA loops into and around the nucleosome, while also challenging earlier concepts about loop formation, the character of the loop and how it propagates. Several complex behaviors were observed, such as reverse translocation and long translocation bursts of the remodeler, without appreciable DNA twist. This review presents and discusses revised models for nucleosome sliding and ejection that integrate this new information with the earlier biochemical studies.Many processes involving chromosomes are guided by DNA-binding proteins, and the access of these proteins to DNA is regulated by chromatin. Nucleosomes, the primary repeating unit of chromatin, package DNA by wrapping 147 base pairs (bp) around an octamer of histone proteins in ∼1.7 helical turns 1-3 . This packaging provides topological order but occludes one face of the DNA, which slows or prevents the recognition of DNA sequences by DNA-binding proteins. To maintain topological order, and also to allow rapid and regulated access to the DNA, cells have evolved a set of chromatin-remodeling machines that alter nucleosome position, presence and structure.Remodelers can be separated into several families on the basis of their composition and activities: SWI/SNF, ISWI, NURD/Mi-2/CHD and the 'split ATPases' INO80 and SWR1 (which bear an insertion within their ATPase domains). Rad54 may represent an additional family, as it perturbs chromatin in vitro, but it apparently lacks specific nucleosome-interacting domains 4,5 . The participation of remodelers in various chromosomal processes has been the subject of many reviews 6-9 . The present work focuses solely on remodeler mechanisms, and primarily on the function of their conserved catalytic subunit, a superfamily 2 (SF2) ATPdependent DNA translocase. Recently, single-molecule approaches have been used to examine several remodelers, providing many new insights into their behavior. Here I discuss these recent studies, compare them with previous biochemical studies and suggest refinements to existing models to account for some of the observations. Remodelers slide, eject and restructure nucleosomesRemodelers can affect nucleosomes in at least four ways ( Fig. 1): (i) sliding, or moving the histone octamer to a new position, which exposes DNA 10-12 ; (ii) ejection, or completely displacing the octamer to expose DNA [13][14][15][16] ; (iii) removal of H2A-H2B dimers, leaving only the central H3-H4 tetramer, which exposes DNA and destabilizes the nucleosome 17,18 ; and (iv) dimer replacement-for example, exchanging the resident H2A-H2B dimers for dimers NIH Public Access

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Section: Remodelers Can Translocate Dna From a Fixed Internal Sitementioning

confidence: 99%

“…Furthermore, SWI/SNF-family remodelers can eject nucleosomes 13,25 , whereas ISWI-family remodelers lack this activity. Specialization is further supported by the different roles and phenotypic effects of remodeler families in vivo 9 . Dimer ejection has been observed with all SWI/SNF remodelers tested, but with only a subset of ISWI remodelers 17,18 .…”

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confidence: 99%

Chromatin remodeling: insights and intrigue from single-molecule studies

Cairns

2007

Nat Struct Mol Biol

227

208

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“…These ATP-dependent remodeling complexes are divided into at least five classes: SWI/SNF, ISWI, CHD(Mi-2), INO80 and SWR1. Each complex has a catalytic ATPase subunit that is critical for allowing or impairing access to nucleosomal DNA to promote or repress gene transcription, respectively (Saha et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Complexes containing BRG1 have been shown to be required for cell cycle control, apoptosis and differentiation in several biological systems (Dunaief et al, 1994;Murphy et al, 1999;Bultman et al, 2000;Reisman et al, 2002;Martens and Winston, 2003;Hendricks et al, 2004;de la Serna et al, 2006). Homozygous knockout mice for the Brg1 gene die during the embryonic stage, whereas heterozygotic survivors are prone to tumors (Bultman et al, 2000;Saha et al, 2006;de la Serna et al, 2006). BRG1 protein can interact with different proteins involved in regulation of transcription, such as factors involved in myeloid, erythrocyte, lymphocyte, muscle, neural and adipocyte commitment and/or differentiation (Dunaief et al, 1994;Murphy et al, 1999;Bultman et al, 2000;Reisman et al, 2002;Martens and Winston, 2003;Hendricks et al, 2004;Saha et al, 2006;de la Serna et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Homozygous knockout mice for the Brg1 gene die during the embryonic stage, whereas heterozygotic survivors are prone to tumors (Bultman et al, 2000;Saha et al, 2006;de la Serna et al, 2006). BRG1 protein can interact with different proteins involved in regulation of transcription, such as factors involved in myeloid, erythrocyte, lymphocyte, muscle, neural and adipocyte commitment and/or differentiation (Dunaief et al, 1994;Murphy et al, 1999;Bultman et al, 2000;Reisman et al, 2002;Martens and Winston, 2003;Hendricks et al, 2004;Saha et al, 2006;de la Serna et al, 2006). The BRG1 chromatin remodeling protein can associate with numerous chromatin-modifying complexes, including transcription co-activators and corepressors.…”

Section: Introductionmentioning

confidence: 99%

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The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

et al. 2010

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We focused our attention on brahma-related gene 1 (BRG1), the ATPase subunit of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex, and analyzed its role in mesenchymal stem cell (MSC) biology. We hypothesized that deviation from the correct concentration of these proteins, which act at the highest level of gene regulation, may be deleterious for cells. We wanted to know what would happen if a cell had to cope with altered regulation of gene expression, either by upregulation or downregulation of BRG1. We assumed that cells would try to restore homeostasis or, alternatively, that the event could trigger senescence/apoptosis phenomena. To this end, in MSCs, we silenced BRG1gene. Knockdown of BRG1 expression induced a significant increase in senescent cells and decrease in apoptotic cells. It is interesting that BRG1 downregulation also induced an increase in heterochromatin. At the molecular level, these phenomena were associated with activation of retinoblastoma-like protein 2 (RB2)/P130-and P53-related pathways. Senescence was accompanied by reduced expression of some stemness-related genes. This is consistent with our previous research, which showed that BRG1 upregulation by ectopic expression also induced senescence processes. Together, these data suggest that BRG1 belongs to a class of genes whose expression is tightly regulated; hence, subtle alterations in BRG1 activity seem to negatively affect mechanisms regulating chromatin status and, in turn, impair cellular physiology.

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Simultaneous Single‐Molecule Mapping of Protein‐DNA Interactions and DNA Methylation by MAPit

Pardo

Darst

Nabilsi

et al. 2011

CP Molecular Biology

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Sites of protein binding to DNA are inferred from footprints or spans of protection against a probing reagent. In most protocols, sites of accessibility to a probe are detected by mapping breaks in DNA strands. As discussed in this unit, such methods obscure molecular heterogeneity by averaging cuts at a given site over all DNA strands in sample population. DNA methyltransferase accessibility protocol for individual templates (MAPit), an alternative method described in this unit, localizes protein-DNA interactions by probing with cytosine-modifying DNA methyltransferases followed by bisulfite sequencing. Sequencing individual DNA products after amplification of bisulfite-converted sequences permits assignment of the methylation status of every enzyme target site along a single DNA strand. Use of the GC-methylating enzyme M.CviPI allows simultaneous mapping of chromatin accessibility and endogenous CpG methylation. MAPit is therefore the only footprinting method that can detect subpopulations of molecules with distinct patterns of protein binding or chromatin architecture, and correlate them directly with the occurrence of endogenous methylation. Additional advantages of MAPit methylation footprinting as well as considerations for experimental design and potential sources of error are discussed.

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Chromatin remodelling: the industrial revolution of DNA around histones

Cited by 511 publications

References 127 publications

Chromatin remodeling: insights and intrigue from single-molecule studies

Chromatin remodeling: insights and intrigue from single-molecule studies

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

Simultaneous Single‐Molecule Mapping of Protein‐DNA Interactions and DNA Methylation by MAPit

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