Chromatin remodelling in mammalian cells by ISWI-type complexes - Where, when and why?

Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum (DKFZ) & BioQuant, Heidelberg, Germany.
FEBS Journal (Impact Factor: 4). 08/2011; 278(19):3608-18. DOI: 10.1111/j.1742-4658.2011.08282.x
Source: PubMed


The specific location of nucleosomes on DNA has important inhibitory or activating roles in the regulation of DNA-dependent processes as it affects the DNA accessibility. Nucleosome positions depend on the ATP-coupled activity of chromatin-remodelling complexes that translocate nucleosomes or evict them from the DNA. The mammalian cell harbors numerous different remodelling complexes that possess distinct activities. These can translate a variety of signals into certain patterns of nucleosome positions with specific functions. Although chromatin remodellers have been extensively studied in vitro, much less is known about how they operate in their cellular environment. Here, we review the cellular activities of the mammalian imitation switch proteins and discuss mechanisms by which they are targeted to sites where their activity is needed.

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Available from: Fabian Erdel,
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    • "Chromatin dynamics play an important role in the plasticity of the DHS landscape since it affects the ability of transcription factors to access potential new regulatory sites and facilitate the loss of unused sites. Although DHSs are stable and perpetuated to daughter cells, they are not necessarily static; they are maintained by a steady state, rapid, and continuous turnover of regulatory factors at specific sites (Narlikar et al. 2002; Erdel and Rippe 2011; Wippo et al. 2011; Calo and Wysocka 2013; Mueller-Planitz et al. 2013; Swygert and Peterson 2014; Voss and Hager 2014). Given the dynamic nature of the DHSs, it could be expected that nucleosome binding proteins known to affect chromatin compaction and accessibility, such as linker histone H1 variants or members of the high mobility group (HMG) families, could play a role in establishing or maintaining the DHS landscape, a possibility that has not yet been examined. "
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    ABSTRACT: DNase I hypersensitive sites (DHSs) are a hallmark of chromatin regions containing regulatory DNA such as enhancers and promoters; however, the factors affecting the establishment and maintenance of these sites are not fully understood. We now show that HMGN1 and HMGN2, nucleosome-binding proteins that are ubiquitously expressed in vertebrate cells, maintain the DHSs landscape of mouse embryonic fibroblasts (MEFs) synergistically. Loss of one of these HMGN variants led to a compensatory increase of binding of the remaining variant. Genome wide mapping of the DHSs in Hmgn1-/-, Hmgn2-/- and Hmgn1-/-n2-/- MEFs reveals that loss of both, but not a single HMGN variant, leads to significant remodeling of the DHSs landscape, especially at enhancer regions marked by H3K4me1 and H3K27ac. Loss of HMGN variants affects the induced expression of stress responsive genes in MEFs, the transcription profiles of several mouse tissues, and leads to altered phenotypes that are not seen in mice lacking only one variant. We conclude that the compensatory binding of HMGN variants to chromatin maintains the DHSs landscape and the transcription fidelity and is necessary to retain wild type phenotypes. Our study provides insights into mechanisms that maintain regulatory sites in chromatin and into functional compensation among nucleosome binding architectural proteins. Published by Cold Spring Harbor Laboratory Press.
    Genome Research 07/2015; 25(9). DOI:10.1101/gr.192229.115 · 14.63 Impact Factor
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    • "Furthermore, some of them, such as the ACF-type complexes that consist minimally of the non-catalytic subunit Acf1 in addition to ISWI, assist nucleosome assembly and introduce a regular spacing into nucleosome arrays in vitro [7]–[12]. In vivo, ISWI complexes are involved in multiple essential nuclear processes, such as transcription regulation, DNA repair, and the maintenance of chromatin higher order structure [13], [14]. Still, how ISWI complexes are targeted and regulated and how their biochemical properties are translated into various biological outcomes remains largely elusive. "
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    ABSTRACT: ISWI is the catalytic subunit of several ATP-dependent chromatin remodelling factors that catalyse the sliding of nucleosomes along DNA and thereby endow chromatin with structural flexibility. Full activity of ISWI requires residues of a basic patch of amino acids in the N-terminal 'tail' of histone H4. Previous studies employing oligopeptides and mononucleosomes suggested that acetylation of the H4 tail at lysine 16 (H4K16) within the basic patch may inhibit the activity of ISWI. On the other hand, the acetylation of H4K16 is known to decompact chromatin fibres. Conceivably, decompaction may enhance the accessibility of nucleosomal DNA and the H4 tail for ISWI interactions. Such an effect can only be evaluated at the level of nucleosome arrays. We probed the influence of H4K16 acetylation on the ATPase and nucleosome sliding activity of Drosophila ISWI in the context of defined, in vitro reconstituted chromatin fibres with physiological nucleosome spacing and linker histone content. Contrary to widespread expectations, the acetylation did not inhibit ISWI activity, but rather stimulated ISWI remodelling under certain conditions. Therefore, the effect of H4K16 acetylation on ISWI remodelling depends on the precise nature of the substrate.
    PLoS ONE 02/2014; 9(2):e88411. DOI:10.1371/journal.pone.0088411 · 3.23 Impact Factor
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    • "Obviously, our data do not preclude that CHD8 also plays a role in repression. Roles as activators and repressors have been described for other remodellers of the SNF2 family and their associated complexes (36,37). "
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