CHRAC/ACF contribute to the repressive ground state of chromatin

Scacchetti, Alessandro; Brueckner, Laura; Jain, Dhawal; Schauer, Tamás; Zhang, Xu; Schnorrer, Frank; Steensel, Bas van; Straub, Tobias; Becker, Peter B.

doi:10.26508/lsa.201800024

Cited by 27 publications

(22 citation statements)

References 46 publications

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“…We then replaced K bp = cK nm in K nm = κK ν bp so to obtain K nm (c) from the data. An intercept between K geom nm (c) and K nm (c) exists for relatively open wrapping angles, typical of open nucleosomes, and with the expected NRL of 182 bp [25] (Fig. 4).…”

Section: Fitted Architecture Parameters Are Compatible With Structuramentioning

confidence: 91%

Polymer coil-globule phase transition is a universal folding principle of Drosophila epigenetic domains

Lesage¹,

Dahirel²,

Victor³

et al. 2018

Preprint

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Localized functional domains within chromosomes, known as topologically associating domains or TADs, have been recently highlighted. In the case of Drosophila, TADs are biochemically defined by epigenetic marks, this suggesting that the 3D arrangement may be the "missing link" between epigenetic coloring and gene activity. Recent observations (Boettiger et al., Nature 2016) on Drosophila fly Kc 167 cell provide access to structural features of these domains with unprecedented resolution thanks to super resolution experiments. In particular, they give access to the distribution of the radii of gyration for domains of different linear length and associated with three different transcriptional activity states: active, inactive or repressed. Intriguingly, the observed scaling laws lacked a consistent interpretation in polymer physics. Our methodology is conceived as to extract the best information from such super-resolution data, and to place these experimental results on a theoretical framework. We show that the experimental data are compatible with the behavior of a finite-sized polymer. The same generic polymer model leads to quantitative differences between active, inactive and repressed domains. Active domains behave as pure polymer coils, while inactive and repressed domains both lie at the coil-globule cross-over. For the first time, both the "color-specificity" of the persistence length and the mean interaction energy were estimated, leading to important differences between epigenetic states.Epigenetic domains|polymer|Drosophila|coil-globule|phase transition T he 3D genome organization inside the cell nucleus is one of the most challenging questions of modern cell biology. Increasing evidence suggests that the complex and dynamical spatial arrangement of chromosomes is a keystone of gene regulation hence cell differentiation. Topologically associating domains (TADs) are one of the emerging features in this field. TADs are identified thanks to chromosome conformation capture techniques and may be defined as genomic regions whose DNA sequences physically interact with each other more frequently than with sequences outside the TAD (1). In Drosophila, these self-interacting genomic regions appear to be biochemically defined by epigenetic marks specific to various gene activity states (2). These states are called colors (3).Obtaining a physical description of the spatial organization of chromatin inside epigenetic domains is then a crucial issue. Traditional optical imaging techniques, however, cannot be used for this purpose, since their resolution is limited by diffraction to a few hundred nanometers while the typical size of epigenetic domains is in the 0.1 to 1 µm range. This limitation has been overcome by the use of super-resolution imaging, as recently achieved notably by Zhuang's and Nollmann's groups. The former used STORM to image Drosophila epigenetic domains at the single-cell level and measured the radius of gyration of each individual snapshot for every imaged domain (4). The latter used SIM to imag...

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Section: Fitted Architecture Parameters Are Compatible With Structuramentioning

confidence: 91%

Polymer coil-globule phase transition is a universal folding principle of Drosophila epigenetic domains

Lesage¹,

Dahirel²,

Victor³

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Either, CHRAC/ACF is somehow locally recruited to these sites to promote the formation of regular chromatin, akin to the specialized action of other remodelers at promoters. Alternatively, CHRAC/ACF might have a more global role in setting up regular spacing as has been suggested before (Fyodorov et al, 2004;Scacchetti et al, 2018). In the latter scenario, the Acf deficiency might affect the regularity of nucleosome arrays throughout the genome, but in the context of our study would only be appreciated at select sites with well-positioned nucleosomes, as regions with poorly positioned nucleosomes cannot be assayed for chromatin regularity in an MNase-seq experiment (Fig.…”

Section: Chrac/acf Has a Global Role In The Formation Of Regular Chromentioning

confidence: 73%

“…Dominant remodelers in preblastoderm embryo extracts are the Imitation SWItch (ISWI) family of remodelers CHRAC, ACF and NURF, which were first identified in this system (Ito et al, 1997;Tsukiyama and Wu, 1995;Varga-Weisz et al, 1997). Among those, the remodelling activity of NURF destroys regularity (Tsukiyama and Wu, 1995), but CHRAC and ACF complexes are prime candidates for contributing to PNA formation, since they promote the formation of regular nucleosome arrays both in vitro and in vivo (Fyodorov et al, 2004;Ito et al, 1997;Scacchetti et al, 2018;Varga-Weisz et al, 1997). To test the influence of CHRAC/ACF on array formation at ATACG sites, we obtained genome-wide nucleosome dyad maps for wildtype and Acf 7 mutant embryos, which do not express Acf (Börner et al, 2016), the signature subunit of CHRAC/ACF (Ito et al, 1997;Varga-Weisz et al, 1997).…”

Section: The Chrac/acf Chromatin Remodeler Contributes To the Formatimentioning

confidence: 99%

“…To explore whether the action of Acf-containing nucleosome sliding factors are observable in reconstituted chromatin we generated DREX from Acf C embryos (where the complete Acf gene is deleted by CRISPR/Cas9 (Scacchetti et al, 2018)) and used it to assemble chromatin on genomic DNA. Mapping nucleosomes and alignment of dyad densities at the ATACG and su(Hw) sites revealed that the positioning of the two nucleosomes directly adjacent to the motifs was very similar in the mutant and the wild type extract (Fig.…”

Section: The Chrac/acf Chromatin Remodeler Contributes To the Formatimentioning

confidence: 99%

“…5C). As we had shown previously that CHRAC/ACF is required for setting up the repressive ground state of chromatin throughout the genome (Scacchetti et al, 2018), we favored the model of a global role of the remodeler.…”

Section: Chrac/acf Has a Global Role In The Formation Of Regular Chromentioning

confidence: 99%

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Genome-wide rules of nucleosome phasing

Baldi

Harpprecht

et al. 2016

Preprint

Self Cite

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Regular successions of positioned nucleosomes -phased nucleosome arrays (PNAs) -are predominantly known from transcriptional start sites (TSS). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSS and strongly enriched for a novel sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the new motif. It also revealed how the global activity of the chromatin remodeler CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro.

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Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death

Kleinberger

2019

FEBS Letters

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The adenovirus (Ad) early region 4 open reading frame 4 (E4orf4) protein is a small 14‐kDa polypeptide endowed with important viral regulatory functions. Although deletion of E4orf4 does not have a major effect on Ad replication due to redundancy among many Ad proteins, E4orf4 provides several functions that improve viral replication. E4orf4 contributes to temporal regulation of virus infection by downregulating early viral gene expression and by altering splicing patterns of Ad mRNAs. It also optimizes the cellular environment for Ad replication by activating the mammalian target of rapamycin pathway to increase viral protein production and by impacting the cell cycle. In addition, E4orf4 participates in the inhibition of the host DNA damage response, promoting the ability of Ad to counteract this antiviral defense mechanism. To fulfill these functions, E4orf4 interacts with numerous cellular proteins, including the major E4orf4 partner, protein phosphatase 2A (PP2A). When expressed alone, outside the context of virus infection, E4orf4 induces an evolutionarily conserved, caspase‐independent, cancer‐selective cell death with many interesting characteristics. This review critically describes E4orf4’s contribution to Ad infection and cancer‐cell death.

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CHRAC/ACF contribute to the repressive ground state of chromatin

Abstract: Chromatin accessibility complex/ATP-utilizing chromatin assembly and remodeling factor help to establish basal transcriptional repression, conceivably through improving the regular spacing of nucleosomes in euchromatin.

Cited by 27 publications

References 46 publications

Polymer coil-globule phase transition is a universal folding principle of Drosophila epigenetic domains

Polymer coil-globule phase transition is a universal folding principle of Drosophila epigenetic domains

Genome-wide rules of nucleosome phasing

Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death

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