The histone chaperone FACT modulates nucleosome structure by tethering its components

Wang, Tao; Liu, Yang; Edwards, Garrett; Krzizike, Daniel D.; Scherman, Hataichanok; Luger, Karolin

doi:10.26508/lsa.201800107

Cited by 74 publications

(57 citation statements)

References 46 publications

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“…The body of KAP1 interactors reflects its recruitment predominantly to the chromatin fraction of the nucleus. In addition to its known partners in heterochromatin formation and transcriptional silencing, such as HP1 proteins and components of the NURD complex, our analysis of the KAP1 interactome in K562 leukaemic cells identified several factors involved in modulating the structure of euchromatin and the activity of RNA polymerases [24,25,[33][34][35][36][37]. This fits with the detection by several studies including ours of KAP1 at the promoters of numerous PolII-transcribed genes.…”

Section: Discussionsupporting

confidence: 88%

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity

Kauzlaric

Jang

Morchikh

et al. 2020

Phil. Trans. R. Soc. B

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KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation, notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To address this paradox, we characterized the protein interactome of KAP1 in the human K562 erythro-leukaemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodellers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited at actively transcribed polymerase II promoters, where its depletion resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.

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Section: Discussionsupporting

confidence: 88%

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity

Kauzlaric

Jang

Morchikh

et al. 2020

Phil. Trans. R. Soc. B

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“…Consistent with a role in transcription, FACT occupancy is generally proportional to the level of transcription (Mason and Struhl 2003;Pelechano et al 2009;Mayer et al 2010;Feng et al 2016). However, this occupancy profile can also be explained by a more passive model in which FACT localization is driven by exposure of its binding sites during any process that disrupts nucleosomes, including transcription (Kemble et al 2015;Tsunaka et al 2016;Martin et al 2018;Wang et al 2018). In this model, FACT's role is to rescue disrupted nucleosomes by reversing the reorganization pathway.…”

mentioning

confidence: 97%

Establishment and Maintenance of Chromatin Architecture Are Promoted Independently of Transcription by the Histone Chaperone FACT and H3-K56 Acetylation in Saccharomyces cerevisiae

et al. 2019

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FACT (FAcilitates Chromatin Transcription/Transactions) is a histone chaperone that can destabilize or assemble nucleosomes. Acetylation of histone H3-K56 weakens a histone-DNA contact that is central to FACT activity, suggesting that this modification could affect FACT functions. We tested this by asking how mutations of H3-K56 and FACT affect nucleosome reorganization activity in vitro, and chromatin integrity and transcript output in vivo. Mimics of unacetylated or permanently acetylated H3-K56 had different effects on FACT activity as expected, but the same mutations had surprisingly similar effects on global transcript levels. The results are consistent with emerging models that emphasize FACT's importance in establishing global chromatin architecture prior to transcription, promoting transitions among different states as transcription profiles change, and restoring chromatin integrity after it is disturbed. Optimal FACT activity required the availability of both modified and unmodified states of H3-K56. Perturbing this balance was especially detrimental for maintaining repression of genes with high nucleosome occupancy over their promoters and for blocking antisense transcription at the +1 nucleosome. The results reveal a complex collaboration between H3-K56 modification status and multiple FACT functions, and support roles for nucleosome reorganization by FACT before, during, and after transcription.

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“…Strains with mutations affecting Mcm2 histone-binding residues suffered from a loss of heterochromatin, highlighting its importance in histone recycling. Crystallography and single molecule assays using optical tweezers show that the SUPT16H subunit of FACT (Spt16 in yeast) can displace and tether nucleosomal H2A-H2B dimers while stabilizing the (H3-H4) 2 tetramer (Chen P. et al, 2018;Wang et al, 2018;Liu et al, 2020). Further structural work showed that MCM2 in turn associates with (H3-H4) 2 surfaces that normally interact with DNA, thereby shielding the tetramer from aberrant interactions (Huang et al, 2015b).…”

Section: Histone Recycling and Tools To Study Interactions At Replicamentioning

confidence: 99%

“…It is, however, important to emphasize that the histone chaperone has since been implicated in numerous other biological events (Gurova et al, 2018). Although first described as an H2A-H2B histone chaperone, it can also bind histones H3 and H4 (Martin et al, 2018;Wang et al, 2018;Mayanagi et al, 2019). FACT allows a controlled assembly and disassembly of nucleosomes in vitro.…”

Section: Histone Dynamics During Gene Transcriptionmentioning

confidence: 99%

Interactions With Histone H3 & Tools to Study Them

Scott

Campos

2020

Front. Cell Dev. Biol.

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Histones are an integral part of chromatin and thereby influence its structure, dynamics, and functions. The effects of histone variants, posttranslational modifications, and binding proteins is therefore of great interest. From the moment that they are deposited on chromatin, nucleosomal histones undergo dynamic changes in function of the cell cycle, and as DNA is transcribed and replicated. In the process, histones are not only modified and bound by various proteins, but also shuffled, evicted, or replaced. Technologies and tools to study such dynamic events continue to evolve and better our understanding of chromatin and of histone proteins proper. Here, we provide an overview of H3.1 and H3.3 histone dynamics throughout the cell cycle, while highlighting some of the tools used to study their protein-protein interactions. We specifically discuss how histones are chaperoned, modified, and bound by various proteins at different stages of the cell cycle. Established and select emerging technologies that furthered (or have a high potential of furthering) our understanding of the dynamic histone-protein interactions are emphasized. This includes experimental tools to investigate spatiotemporal changes on chromatin, the role of histone chaperones, histone posttranslational modifications, and histone-binding effector proteins.

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The histone chaperone FACT modulates nucleosome structure by tethering its components

Abstract: The histone chaperone FACT functions by tethering partial components of the nucleosome, thereby assisting nucleosome disassembly and reassembly during transcription.

Cited by 74 publications

References 46 publications

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity

Establishment and Maintenance of Chromatin Architecture Are Promoted Independently of Transcription by the Histone Chaperone FACT and H3-K56 Acetylation in Saccharomyces cerevisiae

Interactions With Histone H3 & Tools to Study Them

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