scholarly journals Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling

2021 ◽  
Vol 118 (36) ◽  
pp. e2107277118
Author(s):  
Soon-Keat Ooi ◽  
Shigeo Sato ◽  
Chieri Tomomori-Sato ◽  
Ying Zhang ◽  
Zhihui Wen ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Atpase Activity ◽  
Chromatin Remodeling ◽  
Multiple Roles ◽  
Nucleosome Remodeling ◽  
Multiple Functions

The SNF2 family ATPase Amplified in Liver Cancer 1 (ALC1) is the only chromatin remodeling enzyme with a poly(ADP-ribose) (PAR) binding macrodomain. ALC1 functions together with poly(ADP-ribose) polymerase PARP1 to remodel nucleosomes. Activation of ALC1 cryptic ATPase activity and the subsequent nucleosome remodeling requires binding of its macrodomain to PAR chains synthesized by PARP1 and NAD+. A key question is whether PARP1 has a role(s) in ALC1-dependent nucleosome remodeling beyond simply synthesizing the PAR chains needed to activate the ALC1 ATPase. Here, we identify PARP1 separation-of-function mutants that activate ALC1 ATPase but do not support nucleosome remodeling by ALC1. Investigation of these mutants has revealed multiple functions for PARP1 in ALC1-dependent nucleosome remodeling and provides insights into its multifaceted role in chromatin remodeling.

scholarly journals Dependency of ISW1a Chromatin Remodeling on Extranucleosomal DNA

2007 ◽  
Vol 27 (8) ◽  
pp. 3217-3225 ◽  
Author(s):  
Vamsi K. Gangaraju ◽  
Blaine Bartholomew
Keyword(s):  
Atpase Activity ◽  
Chromatin Remodeling ◽  
Molecular Basis ◽  
The Other ◽  
Entry And Exit ◽  
Exit Site ◽  
Optimal Length ◽  
Nucleosome Remodeling ◽  
Dna Footprinting ◽  
Nucleosomal Dna

ABSTRACT The nucleosome remodeling activity of ISW1a was dependent on whether ISW1a was bound to one or both extranucleosomal DNAs. ISW1a preferentially bound nucleosomes with an optimal length of ∼33 to 35 bp of extranucleosomal DNA at both the entry and exit sites over nucleosomes with extranucleosomal DNA at only one entry or exit site. Nucleosomes with extranucleosomal DNA at one of the entry/exit sites were readily remodeled by ISW1a and stimulated the ATPase activity of ISW1a, while conversely, nucleosomes with extranucleosomal DNA at both entry/exit sites were unable either to stimulate the ATPase activity of ISW1a or to be mobilized. DNA footprinting revealed that a major conformational difference between the nucleosomes was the lack of ISW1a binding to nucleosomal DNA two helical turns from the dyad axis in nucleosomes with extranucleosomal DNA at both entry/exit sites. The Ioc3 subunit of ISW1a was found to be the predominant subunit associated with extranucleosomal DNA when ISW1a is bound either to one or to both extranucleosomal DNAs. These two conformations of the ISW1a-nucleosome complex are suggested to be the molecular basis for the nucleosome spacing activity of ISW1a on nucleosomal arrays. ISW1b, the other isoform of ISW1, does not have the same dependency for extranucleosomal DNA as ISW1a and, likewise, is not able to space nucleosomes.

Dynamic epistasis analysis reveals how chromatin remodeling regulates transcriptional bursting

2021 ◽  
Author(s):  
Ineke Brouwer ◽  
Emma Kerklingh ◽  
Fred van Leeuwen ◽  
Tineke L Lenstra
Keyword(s):  
Transcription Factor ◽  
Chromatin Remodeling ◽  
Single Molecule ◽  
Binding Sites ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Nucleosome Remodeling ◽  
Epistasis Analysis ◽  
Transcriptional Bursting ◽  
Kinetics Of

Transcriptional bursting has been linked to the stochastic positioning of nucleosomes. However, how bursting is regulated by remodeling of promoter nucleosomes is unknown. Here, we use single-molecule live-cell imaging of GAL10 transcription in budding yeast to measure how transcriptional bursting changes upon single and double perturbations of chromatin remodeling factors, the transcription factor Gal4 and preinitiation complex (PIC) components. Using dynamic epistasis analysis, we reveal how remodeling of different nucleosomes regulates individual transcriptional bursting parameters. At the nucleosome covering the Gal4 binding sites, RSC acts synergistically with Gal4 binding to facilitate each burst. Conversely, nucleosome remodeling at the TATA box controls only the first burst upon galactose induction. In the absence of remodelers, nucleosomes at canonical TATA boxes are displaced by TBP binding to allow for transcription activation. Overall, our results reveal how promoter nucleosome remodeling, together with transcription factor and PIC binding regulates the kinetics of transcriptional bursting.

scholarly journals RSC2, Encoding a Component of the RSC Nucleosome Remodeling Complex, Is Essential for 2μm Plasmid Maintenance in Saccharomyces cerevisiae

2002 ◽  
Vol 22 (12) ◽  
pp. 4218-4229 ◽  
Author(s):  
Michael C. V. L. Wong ◽  
Suzanna R. S. Scott-Drew ◽  
Matthew J. Hayes ◽  
Philip J. Howard ◽  
James A. H. Murray
Keyword(s):  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Plasmid Dna ◽  
Direct Evidence ◽  
Maternal Inheritance ◽  
Alternative Form ◽  
Nucleosome Remodeling ◽  
Daughter Cells ◽  
Chromatin Remodeling Complex ◽  
Stable Maintenance

ABSTRACT The stable maintenance of the 2μm circle plasmid depends on its ability to overcome intrinsic maternal inheritance bias, which in yeast normally results in the failure to transmit DNA molecules efficiently to daughter cells. In addition to the plasmid proteins Rep1 and Rep2 acting on the plasmid DNA locus STB, it is likely that other chromosomally encoded yeast proteins are required. We have isolated mutants of yeast unable to maintain 2μm and found that RSC2 is essential for 2μm to overcome maternal inheritance bias. Rsc2 is part of a multisubunit RSC chromatin remodeling complex, and we show that in the absence of Rsc2 the chromatin structure of the STB region is significantly altered and the Rep1 protein loses its normal localization to subnuclear foci. Rsc1, a closely related homolog of Rsc2 present in an alternative form of the RSC complex, is not required for 2μm maintenance and does not replace the requirement for Rsc2 when overexpressed. This represents the first specific role for Rsc2 that has been related to a change in chromatin structure, as well as the first direct evidence linking chromatin structure to 2μm segregation.

scholarly journals Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

2015 ◽  
Vol 63 (5) ◽  
pp. 1164-1172 ◽  
Author(s):  
Kouki Nio ◽  
Taro Yamashita ◽  
Hikari Okada ◽  
Mitsumasa Kondo ◽  
Takehiro Hayashi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Chromatin Remodeling ◽  
Human Hepatocellular Carcinoma ◽  
Liver Cancer Stem Cells

Models for chromatin remodeling: a critical comparison

2003 ◽  
Vol 81 (3) ◽  
pp. 169-172 ◽  
Author(s):  
K van Holde ◽  
T Yager
Keyword(s):  
Diffusion Model ◽  
Chromatin Remodeling ◽  
Experimental Studies ◽  
Nucleosome Remodeling ◽  
Defect Generation ◽  
Critical Comparison ◽  
Nucleosomal Dna ◽  
Reptation Model ◽  
Cast Doubt ◽  
Random Diffusion

Nucleosome remodeling has been shown, in many cases, to involve cis displacement of nucleosomes on the DNA. This process seems similar to the long-recognized random diffusion of nucleosomes along DNA, but the remodeling process is unidirectional and ATP dependent. Several years ago, we developed a model for nucleosome migration, based on the diffusion of "twist-defects" within the nucleosomal DNA. This has been modified into a model that incorporates ATP-dependent defect generation, and can account for many observations concerning remodeling. However, certain experimental studies in recent years have cast doubt on the applicability of the twist-diffusion model for remodeling, and seem to favor instead a "reptation" model. We discuss herein these problems and propose a resolution.Key words: nucleosome, remodeling, chromatin.

scholarly journals The Roles of SNF2/SWI2 Nucleosome Remodeling Enzymes in Blood Cell Differentiation and Leukemia

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Punit Prasad ◽  
Andreas Lennartsson ◽  
Karl Ekwall
Keyword(s):  
Blood Cell ◽  
Chromatin Remodeling ◽  
Large Scale ◽  
Cell Development ◽  
Normal Blood ◽  
Aberrant Expression ◽  
Atpase Subunit ◽  
Hematopoietic Stem ◽  
Nucleosome Remodeling ◽  
Genes Encoding

Here, we review the role of sucrose nonfermenting (SNF2) family enzymes in blood cell development. The SNF2 family comprises helicase-like ATPases, originally discovered in yeast, that can remodel chromatin by changing chromatin structure and composition. The human genome encodes 30 different SNF2 enzymes. SNF2 family enzymes are often part of multisubunit chromatin remodeling complexes (CRCs), which consist of noncatalytic/auxiliary subunit along with the ATPase subunit. However, blood cells express a limited set of SNF2 ATPases that are necessary to maintain the pool of hematopoietic stem cells (HSCs) and drive normal blood cell development and differentiation. The composition of CRCs can be altered by the association of specific auxiliary subunits. Several auxiliary CRC subunits have specific functions in hematopoiesis. Aberrant expressions of SNF2 ATPases and/or auxiliary CRC subunit(s) are often observed in hematological malignancies. Using large-scale data from the International Cancer Genome Consortium (ICGC) we observed frequent mutations in genes encoding SNF2 helicase-like enzymes and auxiliary CRC subunits in leukemia. Hence, orderly function of SNF2 family enzymes is crucial for the execution of normal blood cell developmental program, and defects in chromatin remodeling caused by mutations or aberrant expression of these proteins may contribute to leukemogenesis.

scholarly journals Opposing ISWI- and CHD-class chromatin remodeling activities orchestrate heterochromatic DNA repair

2014 ◽  
Vol 207 (6) ◽  
pp. 717-733 ◽  
Author(s):  
Karolin Klement ◽  
Martijn S. Luijsterburg ◽  
Jordan B. Pinder ◽  
Chad S. Cena ◽  
Victor Del Nero ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Replication ◽  
Chromatin Remodeling ◽  
Somatic Mutation ◽  
Strand Break ◽  
Dsb Repair ◽  
Nucleosome Remodeling ◽  
Dna Double Strand Break ◽  
Recruitment System ◽  
Chromatin Relaxation

Heterochromatin is a barrier to DNA repair that correlates strongly with elevated somatic mutation in cancer. CHD class II nucleosome remodeling activity (specifically CHD3.1) retained by KAP-1 increases heterochromatin compaction and impedes DNA double-strand break (DSB) repair requiring Artemis. This obstruction is alleviated by chromatin relaxation via ATM-dependent KAP-1S824 phosphorylation (pKAP-1) and CHD3.1 dispersal from heterochromatic DSBs; however, how heterochromatin compaction is actually adjusted after CHD3.1 dispersal is unknown. In this paper, we demonstrate that Artemis-dependent DSB repair in heterochromatin requires ISWI (imitation switch)-class ACF1–SNF2H nucleosome remodeling. Compacted chromatin generated by CHD3.1 after DNA replication necessitates ACF1–SNF2H–mediated relaxation for DSB repair. ACF1–SNF2H requires RNF20 to bind heterochromatic DSBs, underlies RNF20-mediated chromatin relaxation, and functions downstream of pKAP-1–mediated CHD3.1 dispersal to enable DSB repair. CHD3.1 and ACF1–SNF2H display counteractive activities but similar histone affinities (via the plant homeodomains of CHD3.1 and ACF1), which we suggest necessitates a two-step dispersal and recruitment system regulating these opposing chromatin remodeling activities during DSB repair.

scholarly journals Evidence for DNA Translocation by the ISWI Chromatin-Remodeling Enzyme

2003 ◽  
Vol 23 (6) ◽  
pp. 1935-1945 ◽  
Author(s):  
Iestyn Whitehouse ◽  
Chris Stockdale ◽  
Andrew Flaus ◽  
Mark D. Szczelkun ◽  
Tom Owen-Hughes
Keyword(s):  
Nucleic Acids ◽  
Atpase Activity ◽  
Chromatin Remodeling ◽  
Dna Translocation ◽  
Catalytic Core ◽  
Dna Translocase

ABSTRACT The ISWI proteins form the catalytic core of a subset of ATP-dependent chromatin-remodeling activities. Here, we studied the interaction of the ISWI protein with nucleosomal substrates. We found that the ability of nucleic acids to bind and stimulate the ATPase activity of ISWI depends on length. We also found that ISWI is able to displace triplex-forming oligonucleotides efficiently when they are introduced at sites close to a nucleosome but successively less efficiently 30 to 60 bp from its edge. The ability of ISWI to direct triplex displacement was specifically impeded by the introduction of 5- or 10-bp gaps in the 3′-5′ strand between the triplex and the nucleosome. In combination, these observations suggest that ISWI is a 3′-5′-strand-specific, ATP-dependent DNA translocase that may be capable of forcing DNA over the surface of nucleosomes.

scholarly journals Tension-dependent nucleosome remodeling at the pericentromere in yeast

2012 ◽  
Vol 23 (13) ◽  
pp. 2560-2570 ◽  
Author(s):  
Jolien S. Verdaasdonk ◽  
Ryan Gardner ◽  
Andrew D. Stephens ◽  
Elaine Yeh ◽  
Kerry Bloom
Keyword(s):  
Chromatin Remodeling ◽  
Mitotic Spindle ◽  
Structural Integrity ◽  
Physical Force ◽  
Yeast Saccharomyces Cerevisiae ◽  
Nucleosome Remodeling ◽  
Nucleosome Dynamics ◽  
Chromosome Arm ◽  
Dna Translocase ◽  
Kinetochore Function

Nucleosome positioning is important for the structural integrity of chromosomes. During metaphase the mitotic spindle exerts physical force on pericentromeric chromatin. The cell must adjust the pericentromeric chromatin to accommodate the changing tension resulting from microtubule dynamics to maintain a stable metaphase spindle. Here we examine the effects of spindle-based tension on nucleosome dynamics by measuring the histone turnover of the chromosome arm and the pericentromere during metaphase in the budding yeast Saccharomyces cerevisiae. We find that both histones H2B and H4 exhibit greater turnover in the pericentromere during metaphase. Loss of spindle-based tension by treatment with the microtubule-depolymerizing drug nocodazole or compromising kinetochore function results in reduced histone turnover in the pericentromere. Pericentromeric histone dynamics are influenced by the chromatin-remodeling activities of STH1/NPS1 and ISW2. Sth1p is the ATPase component of the Remodels the Structure of Chromatin (RSC) complex, and Isw2p is an ATP-dependent DNA translocase member of the Imitation Switch (ISWI) subfamily of chromatin-remodeling factors. The balance between displacement and insertion of pericentromeric histones provides a mechanism to accommodate spindle-based tension while maintaining proper chromatin packaging during mitosis.

scholarly journals Transcriptional Suppression by Transient Recruitment of ARIP4 to Sumoylated Nuclear Receptor Ad4BP/SF-1

2009 ◽  
Vol 20 (19) ◽  
pp. 4235-4245 ◽  
Author(s):  
Hidesato Ogawa ◽  
Tomoko Komatsu ◽  
Yasushi Hiraoka ◽  
Ken-ichirou Morohashi
Keyword(s):  
Transcription Factors ◽  
Atpase Activity ◽  
Nuclear Receptors ◽  
Chromatin Remodeling ◽  
Target Genes ◽  
Fine Tuning ◽  
Binding Region ◽  
Interacting Protein ◽  
Double Stranded Dna ◽  
Transcriptional Suppression

The small ubiquitin-like modifier SUMO conjugates transcription factors and suppresses their respective activation of target genes. Although various SUMO-modified transcription factors have been isolated, mechanisms whereby sumoylated-substrates modulate transcription remain unknown. Here, we purified ARIP4 (AR interacting protein 4, a Rad54 family member and a SNF2 chromatin remodeling factor), which interacts with sumoylated Ad4BP/SF-1 through two SUMO-interacting motifs and one Ad4BP/SF-1–binding region. Remarkably, ARIP4 also interacts selectively with other sumoylated nuclear receptors including LRH-1, AR, and GR. Interestingly, the ATPase activity of ARIP4 was stimulated in the presence of sumoylated Ad4BP/SF-1 and the Ad4BP/SF-1–binding site containing double-stranded DNA. ChIP assays and siRNA studies strongly suggested that ARIP4 temporally suppresses Ad4BP/SF-1–mediated transcription through its transient recruitment to target genes. These findings suggest that ARIP4 may be a cofactor that modulates SUMO-mediated fine-tuning of transcriptional suppression.

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