scholarly journals The GBAF chromatin remodeling complex binds H3K27ac and mediates enhancer transcription

2018 ◽  
Author(s):  
Kirill Jefimov ◽  
Nicolas Alcaraz ◽  
Susan L. Kloet ◽  
Signe Värv ◽  
Siri Aastedatter Sakya ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Binding Sites ◽  
Mrna Levels ◽  
Elongation Complex ◽  
Exact Role ◽  
Super Elongation Complex ◽  
Chromatin Remodeling Complex ◽  
Genome Wide ◽  
Enhancer Function ◽  
Interaction Proteomics

AbstractH3K27ac is associated with regulatory active enhancers, but its exact role in enhancer function remains elusive. Using mass spectrometry-based interaction proteomics, we identified the Super Elongation Complex (SEC) and GBAF, a non-canonical GLTSCR1L- and BRD9-containing SWI/SNF chromatin remodeling complex, to be major interactors of H3K27ac. We systematically characterized the composition of GBAF and the conserved GLTSCR1/1L ‘GiBAF’-domain, which we found to be responsible for GBAF complex formation and GLTSCR1L nuclear localization. Inhibition of the bromodomain of BRD9 revealed interaction between GLTSCR1L and H3K27ac to be BRD9-dependent and led to GLTSCR1L dislocation from its preferred binding sites at H3K27ac-associated enhancers. GLTSCR1L disassociation from chromatin resulted in genome-wide downregulation of enhancer transcription while leaving most mRNA expression levels unchanged, except for reduced mRNA levels from loci topologically linked to affected enhancers. Our results indicate that GBAF is an enhancer-associated chromatin remodeler important for transcriptional and regulatory activity of enhancers.Graphical abstract

INO80 requires a polycomb subunit to regulate the establishment of poised chromatin in murine spermatocytes

Development ◽  
2022 ◽  
Vol 149 (1) ◽  
Author(s):  
Prabuddha Chakraborty ◽  
Terry Magnuson
Keyword(s):  
Chromatin Remodeling ◽  
Binding Sites ◽  
Strand Break ◽  
Rna Seq ◽  
Genome Wide Analysis ◽  
The Core ◽  
Chromatin Remodeling Complex ◽  
Genome Wide ◽  
Dna Double Strand Break ◽  
Transcription Program

ABSTRACT INO80 is the catalytic subunit of the INO80-chromatin remodeling complex that is involved in DNA replication, repair and transcription regulation. Ino80 deficiency in murine spermatocytes (Ino80cKO) results in pachytene arrest of spermatocytes due to incomplete synapsis and aberrant DNA double-strand break repair, which leads to apoptosis. RNA-seq on Ino80cKO spermatocytes revealed major changes in transcription, indicating that an aberrant transcription program arises upon INO80 depletion. In Ino80WT spermatocytes, genome-wide analysis showed that INO80-binding sites were mostly promoter proximal and necessary for the regulation of spermatogenic gene expression, primarily of premeiotic and meiotic genes. Furthermore, most of the genes poised for activity, as well as those genes that are active, shared INO80 binding. In Ino80cKO spermatocytes, most poised genes demonstrated de-repression due to reduced H3K27me3 enrichment and, in turn, showed increased expression levels. INO80 interacts with the core PRC2 complex member SUZ12 and promotes its recruitment. Furthermore, INO80 mediates H2A.Z incorporation at the poised promoters, which was reduced in Ino80cKO spermatocytes. Taken together, INO80 is emerging as a major regulator of the meiotic transcription program by mediating poised chromatin establishment through SUZ12 binding.

scholarly journals The Genome-Wide Localization of Rsc9, a Component of the RSC Chromatin-Remodeling Complex, Changes in Response to Stress

2002 ◽  
Vol 9 (3) ◽  
pp. 563-573 ◽  
Author(s):  
Marc Damelin ◽  
Itamar Simon ◽  
Terence I. Moy ◽  
Boris Wilson ◽  
Suzanne Komili ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Chromatin Remodeling Complex ◽  
Genome Wide ◽  
Response To Stress

scholarly journals FOXA2 regulates a network of genes involved in critical functions of human intestinal epithelial cells

2015 ◽  
Vol 47 (7) ◽  
pp. 290-297 ◽  
Author(s):  
Nehal Gosalia ◽  
Rui Yang ◽  
Jenny L. Kerschner ◽  
Ann Harris
Keyword(s):  
Transcription Factors ◽  
Epithelial Cell ◽  
Binding Sites ◽  
Intestinal Epithelial Cell ◽  
Cell Function ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Membrane Function ◽  
Protein Levels ◽  
Genome Wide

The forkhead box A (FOXA) family of pioneer transcription factors is critical for the development of many endoderm-derived tissues. Their importance in regulating biological processes in the lung and liver is extensively characterized, though much less is known about their role in intestine. Here we investigate the contribution of FOXA2 to coordinating intestinal epithelial cell function using postconfluent Caco2 cells, differentiated into an enterocyte-like model. FOXA2 binding sites genome-wide were determined by ChIP-seq and direct targets of the factor were validated by ChIP-qPCR and siRNA-mediated depletion of FOXA1/2 followed by RT-qPCR. Peaks of FOXA2 occupancy were frequent at loci contributing to gene ontology pathways of regulation of cell migration, cell motion, and plasma membrane function. Depletion of both FOXA1 and FOXA2 led to a significant reduction in the expression of multiple transmembrane proteins including ion channels and transporters, which form a network that is essential for maintaining normal ion and solute transport. One of the targets was the adenosine A2B receptor, and reduced receptor mRNA levels were associated with a functional decrease in intracellular cyclic AMP. We also observed that 30% of FOXA2 binding sites contained a GATA motif and that FOXA1/A2 depletion reduced GATA-4, but not GATA-6 protein levels. These data show that FOXA2 plays a pivotal role in regulating intestinal epithelial cell function. Moreover, that the FOXA and GATA families of transcription factors may work cooperatively to regulate gene expression genome-wide in the intestinal epithelium.

scholarly journals Identification of SWI2/SNF2-Related 1 Chromatin Remodeling Complex (SWR1-C) Subunits in Pineapple and the Role of Pineapple SWR1 COMPLEX 6 (AcSWC6) in Biotic and Abiotic Stress Response

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 364 ◽  
Author(s):  
Jakada ◽  
Aslam ◽  
Fakher ◽  
Greaves ◽  
Li ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Chromatin Remodeling ◽  
Sequence Similarity ◽  
Rna Seq ◽  
Abiotic Stress Response ◽  
Biotic And Abiotic Stress ◽  
Enhanced Resistance ◽  
Chromatin Remodeling Complex ◽  
Genome Wide

Chromatin remodeling complex orchestrates numerous aspects of growth and development in eukaryotes. SWI2/SNF2-Related 1 chromatin remodeling complex (SWR1-C) is a member of the SWI/SNF ATPase-containing chromatin remodeling complex responsible for the exchange of H2A for H2A.Z. In plants, SWR1-C plays a crucial role by transcriptionally regulating numerous biological and developmental processes. However, SWR1-C activity remains obscure in pineapple. Here, we aim to identify the SWR1-C subunits in pineapple. By genome-wide identification, we found a total of 11 SWR1-C subunits in the pineapple. The identified SWR1-C subunits were named and classified based on the sequence similarity and phylogenetic analysis. RNA-Seq analysis showed that pineapple SWR1-C subunits are expressed differentially in different organs and at different stages. Additionally, the qRT-PCR of pineapple SWR1-C subunits during abiotic stress exposure showed significant changes in their expression. We further investigated the functions of pineapple SWR1 COMPLEX 6 (AcSWC6) by ectopically expressing it in Arabidopsis. Interestingly, transgenic plants ectopically expressing AcSWC6 showed susceptibility to fungal infection and enhanced resistance to salt and osmotic stress, revealing its involvement in biotic and abiotic stress. Moreover, the complementation of mutant Arabidopsis swc6 by pineapple SWC6 suggested the conserved function of SWC6 in plants.

scholarly journals SWI/SNF Displaces SAGA-Acetylated Nucleosomes

2006 ◽  
Vol 5 (10) ◽  
pp. 1738-1747 ◽  
Author(s):  
Mark Chandy ◽  
José L. Gutiérrez ◽  
Philippe Prochasson ◽  
Jerry L. Workman
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase ◽  
Histone Acetylation ◽  
Chromatin Remodeling ◽  
Binding Sites ◽  
Saga Complex ◽  
Chromatin Remodeling Complex ◽  
Nucleosome Array ◽  
Transcription Activators

ABSTRACT SWI/SNF is a well-characterized chromatin remodeling complex that remodels chromatin by sliding nucleosomes in cis and/or displacing nucleosomes in trans. The latter mechanism has the potential to remove promoter nucleosomes, allowing access to transcription factors and RNA polymerase. In vivo, histone acetylation often precedes apparent nucleosome loss; therefore, we sought to determine whether nucleosomes containing acetylated histones could be displaced by the SWI/SNF chromatin remodeling complex. We found that SAGA-acetylated histones were lost from an immobilized nucleosome array when treated with the SWI/SNF complex. When the nucleosome array was acetylated by SAGA in the presence of bound transcription activators, it generated a peak of acetylation surrounding the activator binding sites. Subsequent SWI/SNF treatment suppressed this acetylation peak. Immunoblots indicated that SWI/SNF preferentially displaced acetylated histones from the array relative to total histones. Moreover, the Swi2/Snf2 bromodomain, an acetyl-lysine binding domain, played a role in the displacement of acetylated histones. These data indicate that targeted histone acetylation by the SAGA complex predisposes promoter nucleosomes for displacement by the SWI/SNF complex.

scholarly journals Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection

2020 ◽  
Author(s):  
Jin Wei ◽  
Mia Madel Alfajaro ◽  
Ruth E. Hanna ◽  
Peter C. DeWeirdt ◽  
Madison S. Strine ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Cathepsin L ◽  
Therapeutic Targets ◽  
Chromatin Remodeling Complex ◽  
Genome Wide ◽  
A Genome ◽  
Viral Genes ◽  
Crispr Screen ◽  
Chaperone Complex ◽  
Host Genes

Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 and identified known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex and key components of the TGF-β signaling pathway. Small molecule inhibitors of these pathways prevented SARS-CoV-2-induced cell death. We also revealed that the alarmin HMGB1 is critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.

scholarly journals The NuRD chromatin–remodeling complex regulates signaling and repair of DNA damage

2010 ◽  
Vol 190 (5) ◽  
pp. 741-749 ◽  
Author(s):  
Godelieve Smeenk ◽  
Wouter W. Wiegant ◽  
Hans Vrolijk ◽  
Aldo P. Solari ◽  
Albert Pastink ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chromatin Remodeling ◽  
Cell Cycle Progression ◽  
Histone Deacetylation ◽  
Dna Double Strand Breaks ◽  
Nucleosome Remodeling ◽  
Chromatin Remodeling Complex ◽  
Genome Wide ◽  
A Genome ◽  
A Subunit

Cells respond to ionizing radiation (IR)–induced DNA double-strand breaks (DSBs) by orchestrating events that coordinate cell cycle progression and DNA repair. How cells signal and repair DSBs is not yet fully understood. A genome-wide RNA interference screen in Caenorhabditis elegans identified egr-1 as a factor that protects worm cells against IR. The human homologue of egr-1, MTA2 (metastasis-associated protein 2), is a subunit of the nucleosome-remodeling and histone deacetylation (NuRD) chromatin-remodeling complex. We show that knockdown of MTA2 and CHD4 (chromodomain helicase DNA-binding protein 4), the catalytic subunit (adenosine triphosphatase [ATPase]) of NuRD, leads to accumulation of spontaneous DNA damage and increased IR sensitivity. MTA2 and CHD4 accumulate in DSB-containing chromatin tracks generated by laser microirradiation. Directly at DSBs, CHD4 stimulates RNF8/RNF168-dependent formation of ubiquitin conjugates to facilitate the accrual of RNF168 and BRCA1. Finally, we show that CHD4 promotes DSB repair and checkpoint activation in response to IR. Thus, the NuRD chromatin–remodeling complex is a novel regulator of DNA damage responses that orchestrates proper signaling and repair of DSBs.

scholarly journals SWR1 Chromatin Remodeling Complex Prevents Mitotic Slippage during Spindle Position Checkpoint Arrest

2019 ◽  
Author(s):  
Ayse Koca Caydasi ◽  
Anton Khmelinskii ◽  
Zoulfia Darieva ◽  
Bahtiyar Kurtulmus ◽  
Michael Knop ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromatin Remodeling ◽  
Daughter Cell ◽  
Budding Yeast ◽  
Genetic Material ◽  
Chromatin Remodeling Complex ◽  
Mitotic Slippage ◽  
Genome Wide ◽  
Surveillance Mechanism ◽  
Spindle Position

ABSTRACTFaithful chromosome segregation in budding yeast requires correct positioning of the mitotic spindle along the mother to daughter cell polarity axis. When the anaphase spindle is not correctly positioned, a surveillance mechanism, named as the spindle position checkpoint (SPOC), prevents the progression out of mitosis until correct spindle positioning is achieved. How SPOC works on a molecular level is not well-understood. Here, we performed a genome-wide genetic screen to search for components required for SPOC. We identified the SWR1 chromatin-remodeling complex (SWR1-C) among the several novel factors that are essential for SPOC integrity. Cells lacking SWR1-C were able to activate SPOC upon spindle misorientation but underwent mitotic slippage upon prolonged SPOC arrest. This mitotic slippage required the Cdc14-early anaphase release pathway and other factors including the SAGA histone acetyltransferase complex, proteasome components, the mitotic cyclin-dependent kinase inhibitor Sic1 and the mitogen-activated protein kinase Slt2/Mpk1. Together, our data establish a novel link between chromatin remodeling and robust checkpoint arrest in late anaphase.AUTHORS SUMMARYBefore it physically divides into two, the cell must duplicate its genetic material and separate the duplicated copies to the opposite poles of the cell with the help of the spindle machinery. The direction along which the genetic material is separated has different consequences on cell division, especially when the opposite poles of the cell differ from each other, as is the case of asymmetric cell division. Every cell division in budding yeast is asymmetric. The new (daughter) cell grows on the old (mother) cell and pinches of from this location at the end of the cell division, giving rise to a new and an old cell. The daughter and mother cells differ in size and composition, thus the cell division is asymmetric. In order for the daughter cell to receive one copy of the duplicated genetic material, budding yeast has to separate the copies of its genetic material along the mother to daughter cell direction, which is possible by placing the spindle apparatus along this direction.A surveillance mechanism named the Spindle Position Checkpoint (SPOC) in budding yeast monitors the position of the mitotic spindle and prevents cells from dividing if the spindle fails to align in the mother to daughter direction. The cell can resume cell division only after correcting the position of the spindle followed by inactivation of SPOC. This way SPOC prevents multi-nucleation and enucleation, and hence it is a crucial mechanism to maintain the correct ploidy. It has been known that about five proteins play a role in positively supporting the SPOC. Yet, how SPOC works on a molecular level remains ill understood.In this study, we aimed to find out novel components of SPOC. Through an unbiased genome-wide genetic screen, we successfully identified several new components of the SPOC machinery. Among several other novel proteins identified, we investigated the role of the SWR1 chromatin remodeling complex (SWR1-C) in more detail. We show that the SWR1-C has a function in preventing cells with mis-positioned spindles from resuming cell division when the spindle stays mis-positioned for a prolonged time (mitotic slippage). Our data indicated that SWR1-C is not required to start the immediate SPOC response, rather it is important to keep the prolonged SPOC arrest.

scholarly journals Derepression of INO1 Transcription Requires Cooperation between the Ino2p-Ino4p Heterodimer and Cbf1p and Recruitment of the ISW2 Chromatin-Remodeling Complex

2010 ◽  
Vol 9 (12) ◽  
pp. 1845-1855 ◽  
Author(s):  
Ameet Shetty ◽  
John M. Lopes
Keyword(s):  
Chromatin Remodeling ◽  
Binding Sites ◽  
De Novo ◽  
Bhlh Protein ◽  
Promoter Element ◽  
Content Type ◽  
Reading Frame ◽  
Helix Loop Helix ◽  
Chromatin Remodeling Complex ◽  
Binding Factor

ABSTRACT The Saccharomyces cerevisiae INO1 gene encodes the structural enzyme inositol-3-phosphate synthase for the synthesis de novo of inositol and inositol-containing phospholipids. The transcription of INO1 is completely derepressed in the absence of inositol and choline (I− C−). Derepression requires the binding of the Ino2p-Ino4p basic helix-loop-helix (bHLH) heterodimer to the UAS INO promoter element. We report here the requirement of a third bHLH protein, centromere-binding factor 1 (Cbf1p), for the complete derepression of INO1 transcription. We found that Cbf1p regulates INO1 transcription by binding to sites distal to the INO1 promoter and encompassing the upstream SNA3 open reading frame (ORF) and promoter. The binding of Cbf1p requires Ino2p-Ino4p binding to the UAS INO sites in the INO1 promoter and vice versa, suggesting a cooperative mechanism. Furthermore, Cbf1p binding to the upstream sites was required for the binding of the ISW2 chromatin-remodeling complex to the Ino2p-Ino4p-binding sites on the INO1 promoter. Consistent with this, ISW2 was also required for the complete derepression of INO1 transcription.

scholarly journals NC2 complex is a key factor for the activation of catalase-3 transcription by regulating H2A.Z deposition

2020 ◽  
Vol 48 (15) ◽  
pp. 8332-8348
Author(s):  
Guofei Cui ◽  
Qing Dong ◽  
Jiabin Duan ◽  
Chengcheng Zhang ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Gene Transcription ◽  
Transcriptional Activation ◽  
Negative Regulator ◽  
Exact Role ◽  
Histone Fold ◽  
Chromatin Remodeling Complex ◽  
Key Factor ◽  
Repression Domain

Abstract Negative cofactor 2 (NC2), including two subunits NC2α and NC2β, is a conserved positive/negative regulator of class II gene transcription in eukaryotes. It is known that NC2 functions by regulating the assembly of the transcription preinitiation complex. However, the exact role of NC2 in transcriptional regulation is still unclear. Here, we reveal that, in Neurospora crassa, NC2 activates catalase-3 (cat-3) gene transcription in the form of heterodimer mediated by histone fold (HF) domains of two subunits. Deletion of HF domain in either of two subunits disrupts the NC2α–NC2β interaction and the binding of intact NC2 heterodimer to cat-3 locus. Loss of NC2 dramatically increases histone variant H2A.Z deposition at cat-3 locus. Further studies show that NC2 recruits chromatin remodeling complex INO80C to remove H2A.Z from the nucleosomes around cat-3 locus, resulting in transcriptional activation of cat-3. Besides HF domains of two subunits, interestingly, C-terminal repression domain of NC2β is required not only for NC2 binding to cat-3 locus, but also for the recruitment of INO80C to cat-3 locus and removal of H2A.Z from the nucleosomes. Collectively, our findings reveal a novel mechanism of NC2 in transcription activation through recruiting INO80C to remove H2A.Z from special H2A.Z-containing nucleosomes.

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