5,083 results match your criteria atpase chromatin

SOX4 and SMARCA4 cooperatively regulate PI3k signaling through transcriptional activation of TGFBR2.

NPJ Breast Cancer 2021 Apr 9;7(1):40. Epub 2021 Apr 9.

Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Dysregulation of PI3K/Akt signaling is a dominant feature in basal-like or triple-negative breast cancers (TNBC). However, the mechanisms regulating this pathway are largely unknown in this subset of aggressive tumors. Here we demonstrate that the transcription factor SOX4 is a key regulator of PI3K signaling in TNBC. Read More

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Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm.

Proc Natl Acad Sci U S A 2021 Mar;118(12)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029;

Specification of Sox2 proneurosensory progenitors within otic ectoderm is a prerequisite for the production of sensory cells and neurons for hearing. However, the underlying molecular mechanisms driving this lineage specification remain unknown. Here, we show that the Brg1-based SWI/SNF chromatin-remodeling complex interacts with the neurosensory-specific transcriptional regulators Eya1/Six1 to induce expression and promote proneurosensory-lineage specification. Read More

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Pontin Functions as A Transcriptional Co-activator for Retinoic Acid-induced HOX Gene Expression.

J Mol Biol 2021 Mar 11:166928. Epub 2021 Mar 11.

Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address:

Pontin is a AAA+ ATPase protein that has functions in various biological contexts including gene transcription regulation, chromatin remodeling, DNA damage sensing and repair, as well as assembly of protein and ribonucleoprotein complexes. Pontin is known to regulate the transcription of several important signaling pathways, including Wnt signaling. However, its role in early embryonic signaling regulation remains unclear. Read More

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Getting there: understanding the chromosomal recruitment of the AAA+ ATPase Pch2/TRIP13 during meiosis.

Curr Genet 2021 Mar 12. Epub 2021 Mar 12.

Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.

The generally conserved AAA+ ATPase Pch2/TRIP13 is involved in diverse aspects of meiosis, such as prophase checkpoint function, DNA break regulation, and meiotic recombination. The controlled recruitment of Pch2 to meiotic chromosomes allows it to use its ATPase activity to influence HORMA protein-dependent signaling. Because of the connection between Pch2 chromosomal recruitment and its functional roles in meiosis, it is important to reveal the molecular details that govern Pch2 localization. Read More

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Interplay of BAF and MLL4 promotes cell type-specific enhancer activation.

Nat Commun 2021 03 12;12(1):1630. Epub 2021 Mar 12.

Adipocyte Biology and Gene Regulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.

Cell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF chromatin remodeling complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Read More

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Emerging oncogene ATAD2: Signaling cascades and therapeutic initiatives.

Life Sci 2021 Mar 9;276:119322. Epub 2021 Mar 9.

Biochemistry and Cell Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha 752050, India. Electronic address:

ATAD2 is a promising oncoprotein with tumor-promoting functions in many cancers. It is a valid cancer drug-target and a potential cancer-biomarker for multiple malignancies. As a cancer/testis antigen (CTA), ATAD2 could also be a probable candidate for immunotherapy. Read More

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The Role of Non-Catalytic Domains of Hrp3 in Nucleosome Remodeling.

Int J Mol Sci 2021 Feb 11;22(4). Epub 2021 Feb 11.

Department of Biosciences and Nutrition, Karolinska Institutet NEO, 141 83 Huddinge, Sweden.

The Helicase-related protein 3 (Hrp3), an ATP-dependent chromatin remodeling enzyme from the CHD family, is crucial for maintaining global nucleosome occupancy in (. Although the ATPase domain of Hrp3 is essential for chromatin remodeling, the contribution of non-ATPase domains of Hrp3 is still unclear. Here, we investigated the role of non-ATPase domains using in vitro methods. Read More

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February 2021

Diversity roles of CHD1L in normal cell function and tumorigenesis.

Biomark Res 2021 Mar 4;9(1):16. Epub 2021 Mar 4.

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, China.

Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a multifunctional protein participated in diverse cellular processes, including chromosome remodeling, cell differentiation and development. CHD1L is a regulator of chromosomal integrity maintenance, DNA repair and transcriptional regulation through its bindings to DNA. By regulating kinds of complex networks, CHD1L has been identified as a potent anti-apoptotic and pro-proliferative factor. Read More

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CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.

Mol Cells 2021 Feb;44(2):101-115

Department of Life Science, Ewha Womans University, Seoul 03760, Korea.

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression. Read More

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February 2021

Single-Molecule Imaging Reveals the Mechanism Underlying Histone Loading of AAA+ ATPase Abo1.

Mol Cells 2021 Feb;44(2):79-87

Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.

Chromatin dynamics is essential for maintaining genomic integrity and regulating gene expression. Conserved bromodomain-containing AAA+ ATPases play important roles in nucleosome organization as histone chaperones. Recently, the high-resolution cryo-electron microscopy structures of Abo1 revealed that it forms a hexameric ring and undergoes a conformational change upon ATP hydrolysis. Read More

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February 2021

The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution.

Sci Rep 2021 Feb 18;11(1):4195. Epub 2021 Feb 18.

Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Building 6A Room 2A02, 6 Center Drive, Bethesda, MD, 20892, USA.

Isw1 and Chd1 are ATP-dependent nucleosome-spacing enzymes required to establish regular arrays of phased nucleosomes near transcription start sites of yeast genes. Cells lacking both Isw1 and Chd1 have extremely disrupted chromatin, with weak phasing, irregular spacing and a propensity to form close-packed dinucleosomes. The Isw1 ATPase subunit occurs in two different remodeling complexes: ISW1a (composed of Isw1 and Ioc3) and ISW1b (composed of Isw1, Ioc2 and Ioc4). Read More

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February 2021

SMARCA2 Is a Novel Interactor of NSD2 and Regulates Prometastatic through Chromatin Remodeling in t(4;14) Multiple Myeloma.

Cancer Res 2021 Feb 18. Epub 2021 Feb 18.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

NSD2 is the primary oncogenic driver in t(4;14) multiple myeloma. Using SILAC-based mass spectrometry, we demonstrate a novel role of NSD2 in chromatin remodeling through its interaction with the SWI/SNF ATPase subunit SMARCA2. SMARCA2 was primarily expressed in t(4;14) myeloma cells, and its interaction with NSD2 was noncanonical and independent of the SWI/SNF complex. Read More

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February 2021

CUL2 , TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle.

EMBO Rep 2021 Mar 15;22(3):e52164. Epub 2021 Feb 15.

The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK.

The eukaryotic replisome is disassembled in each cell cycle, dependent upon ubiquitylation of the CMG helicase. Studies of Saccharomyces cerevisiae, Caenorhabditis elegans and Xenopus laevis have revealed surprising evolutionary diversity in the ubiquitin ligases that control CMG ubiquitylation, but regulated disassembly of the mammalian replisome has yet to be explored. Here, we describe a model system for studying the ubiquitylation and chromatin extraction of the mammalian CMG replisome, based on mouse embryonic stem cells. Read More

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Current and emerging roles of Cockayne syndrome group B (CSB) protein.

Nucleic Acids Res 2021 03;49(5):2418-2434

Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

Cockayne syndrome (CS) is a segmental premature aging syndrome caused primarily by defects in the CSA or CSB genes. In addition to premature aging, CS patients typically exhibit microcephaly, progressive mental and sensorial retardation and cutaneous photosensitivity. Defects in the CSB gene were initially thought to primarily impair transcription-coupled nucleotide excision repair (TC-NER), predicting a relatively consistent phenotype among CS patients. Read More

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Acute BAF perturbation causes immediate changes in chromatin accessibility.

Nat Genet 2021 03 8;53(3):269-278. Epub 2021 Feb 8.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Cancer-associated, loss-of-function mutations in genes encoding subunits of the BRG1/BRM-associated factor (BAF) chromatin-remodeling complexes often cause drastic chromatin accessibility changes, especially in important regulatory regions. However, it remains unknown how these changes are established over time (for example, immediate consequences or long-term adaptations), and whether they are causative for intracomplex synthetic lethalities, abrogating the formation or activity of BAF complexes. In the present study, we use the dTAG system to induce acute degradation of BAF subunits and show that chromatin alterations are established faster than the duration of one cell cycle. Read More

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Mammalian SWI/SNF continuously restores local accessibility to chromatin.

Nat Genet 2021 03 8;53(3):279-287. Epub 2021 Feb 8.

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Chromatin accessibility is a hallmark of regulatory regions, entails transcription factor (TF) binding and requires nucleosomal reorganization. However, it remains unclear how dynamic this process is. In the present study, we use small-molecule inhibition of the catalytic subunit of the mouse SWI/SNF remodeler complex to show that accessibility and reduced nucleosome presence at TF-binding sites rely on persistent activity of nucleosome remodelers. Read More

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DEAD-box polypeptide 43 facilitates piRNA amplification by actively liberating RNA from Ago3-piRISC.

EMBO Rep 2021 Apr 8;22(4):e51313. Epub 2021 Feb 8.

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.

The piRNA amplification pathway in Bombyx is operated by Ago3 and Siwi in their piRISC form. The DEAD-box protein, Vasa, facilitates Ago3-piRISC production by liberating cleaved RNAs from Siwi-piRISC in an ATP hydrolysis-dependent manner. However, the Vasa-like factor facilitating Siwi-piRISC production along this pathway remains unknown. Read More

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Evolutionary Conservation of Structural and Functional Coupling between the BRM AT-Hook and Bromodomain.

J Mol Biol 2021 Feb 2:166845. Epub 2021 Feb 2.

University of Iowa, Carver College of Medicine, Department of Biochemistry, Iowa City, IA 52242, United States; University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, Aurora, CO 80045, United States. Electronic address:

The BAF chromatin remodeling complex is critical for genome regulation. The central ATPase of BAF is either BRM or BRG1, both of which contain a C-terminal bromodomain, known to associate with acetylated lysines. We have recently demonstrated that in addition to acetyl-lysine binding, the BRG1/BRM bromodomain can associate with DNA through a lysine/arginine rich patch that is adjacent to the acetyl-lysine binding pocket. Read More

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February 2021

Comparative proteomic analysis of kinesin-8B deficient Plasmodium berghei during gametogenesis.

J Proteomics 2021 Mar 21;236:104118. Epub 2021 Jan 21.

Laboratory of Protein Chemistry and Biochemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, Brasilia 70910-900, Brazil. Electronic address:

Plasmodium blood stages, responsible for human to vector transmission, termed gametocytes, are the precursor cells that develop into gametes in the mosquito. Male gametogenesis works as a bottleneck for the parasite life cycle, where, during a peculiar and rapid exflagellation, a male gametocyte produces 8 intracellular axonemes that generate by budding 8 motile gametes. Understanding the molecular mechanisms of gametogenesis is key to design strategies for controlling malaria transmission. Read More

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Single-strand DNA breaks cause replisome disassembly.

Mol Cell 2021 03 22;81(6):1309-1318.e6. Epub 2021 Jan 22.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA. Electronic address:

DNA damage impedes replication fork progression and threatens genome stability. Upon encounter with most DNA adducts, the replicative CMG helicase (CDC45-MCM2-7-GINS) stalls or uncouples from the point of synthesis, yet eventually resumes replication. However, little is known about the effect on replication of single-strand breaks or "nicks," which are abundant in mammalian cells. Read More

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p53 affects epigenetic signature on SOCS1 promoter in response to TLR4 inhibition.

Cytokine 2021 Apr 18;140:155418. Epub 2021 Jan 18.

National Brain Research Centre, Manesar, Haryana 122 052, India. Electronic address:

Suppressor of cytokine signaling (SOCS1) functions as a negative regulator of toll-like receptor (TLR) induced inflammatory signaling. As silencing of SOCS1 is concomitant with elevated TLR4 levels in glioblastoma, we investigated the effect of TLR4 inhibition on SOCS1 expression. Pharmacological inhibition of TLR4 signaling by TAK242 or its siRNA-mediated knockdown in p53 mutant or wild-type glioma cells resulted in either increased or decreased SOCS1 expression and promoter activity, respectively. Read More

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Autoinhibitory elements of the Chd1 remodeler block initiation of twist defects by destabilizing the ATPase motor on the nucleosome.

Proc Natl Acad Sci U S A 2021 Jan;118(4)

Thomas C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218

Chromatin remodelers are ATP (adenosine triphosphate)-powered motors that reposition nucleosomes throughout eukaryotic chromosomes. Remodelers possess autoinhibitory elements that control the direction of nucleosome sliding, but underlying mechanisms of inhibition have been unclear. Here, we show that autoinhibitory elements of the yeast Chd1 remodeler block nucleosome sliding by preventing initiation of twist defects. Read More

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January 2021

IMITATION SWITCH is required for normal chromatin structure and gene repression in PRC2 target domains.

Proc Natl Acad Sci U S A 2021 Jan;118(4)

Department of Microbiology, University of Georgia, Athens, GA 30602;

Polycomb Group (PcG) proteins are part of an epigenetic cell memory system that plays essential roles in multicellular development, stem cell biology, X chromosome inactivation, and cancer. In animals, plants, and many fungi, Polycomb Repressive Complex 2 (PRC2) catalyzes trimethylation of histone H3 lysine 27 (H3K27me3) to assemble transcriptionally repressed facultative heterochromatin. PRC2 is structurally and functionally conserved in the model fungus , and recent work in this organism has generated insights into PRC2 control and function. Read More

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January 2021

ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells.

Nat Cell Biol 2021 02 18;23(2):160-171. Epub 2021 Jan 18.

Department of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

The response to poly(ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair and the abundance of lesions that trap PARP enzymes. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR-based screen, we identified the PAR-binding chromatin remodeller ALC1/CHD1L as a key determinant of PARPi toxicity in HR-deficient cells. Read More

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February 2021

Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters.

Mol Cell 2021 02 15;81(4):830-844.e13. Epub 2021 Jan 15.

Theodor Boveri Institute, Department of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, 97074 Würzburg, Germany. Electronic address:

The MYC oncoprotein globally affects the function of RNA polymerase II (RNAPII). The ability of MYC to promote transcription elongation depends on its ubiquitylation. Here, we show that MYC and PAF1c (polymerase II-associated factor 1 complex) interact directly and mutually enhance each other's association with active promoters. Read More

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February 2021

Comparison of loop extrusion and diffusion capture as mitotic chromosome formation pathways in fission yeast.

Nucleic Acids Res 2021 02;49(3):1294-1312

Chromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UK.

Underlying higher order chromatin organization are Structural Maintenance of Chromosomes (SMC) complexes, large protein rings that entrap DNA. The molecular mechanism by which SMC complexes organize chromatin is as yet incompletely understood. Two prominent models posit that SMC complexes actively extrude DNA loops (loop extrusion), or that they sequentially entrap two DNAs that come into proximity by Brownian motion (diffusion capture). Read More

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February 2021

G6PD activity contributes to the regulation of histone acetylation and gene expression in smooth muscle cells and to the pathogenesis of vascular diseases.

Am J Physiol Heart Circ Physiol 2021 03 8;320(3):H999-H1016. Epub 2021 Jan 8.

Department of Pharmacology, New York Medical College, Valhalla, New York.

We aimed to determine ) the mechanism(s) that enables glucose-6-phosphate dehydrogenase (G6PD) to regulate serum response factor (SRF)- and myocardin (MYOCD)-driven smooth muscle cell (SMC)-restricted gene expression, a process that aids in the differentiation of SMCs, and ) whether G6PD-mediated metabolic reprogramming contributes to the pathogenesis of vascular diseases in metabolic syndrome (MetS). Inhibition of G6PD activity increased (>30%) expression of SMC-restricted genes and concurrently decreased (40%) the growth of human and rat SMCs ex vivo. Expression of SMC-restricted genes decreased (>100-fold) across successive passages in primary cultures of SMCs isolated from mouse aorta. Read More

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Sequence and functional differences in the ATPase domains of CHD3 and SNF2H promise potential for selective regulability and drugability.

FEBS J 2021 Jan 5. Epub 2021 Jan 5.

Department of Biochemistry, Genetics and Microbiology, Biochemistry III, University of Regensburg, Germany.

Chromatin remodelers use the energy of ATP hydrolysis to regulate chromatin dynamics. Their impact for development and disease requires strict enzymatic control. Here, we address the differential regulability of the ATPase domain of hSNF2H and hCHD3, exhibiting similar substrate affinities and enzymatic activities. Read More

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January 2021

Biophysics of Chromatin Remodeling.

Annu Rev Biophys 2021 Jan 4. Epub 2021 Jan 4.

T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA; email:

As primary carriers of epigenetic information and gatekeepers of genomic DNA, nucleosomes are essential for proper growth and development of all eukaryotic cells. Although they are intrinsically dynamic, nucleosomes are actively reorganized by ATP-dependent chromatin remodelers. Chromatin remodelers contain helicase-like ATPase motor domains that can translocate along DNA, and a long-standing question in the field is how this activity is used to reposition or slide nucleosomes. Read More

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January 2021

Chromatin structure restricts origin utilization when quiescent cells re-enter the cell cycle.

Nucleic Acids Res 2021 01;49(2):864-878

Department of Molecular Genetics and Microbiology University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.

Quiescent cells reside in G0 phase, which is characterized by the absence of cell growth and proliferation. These cells remain viable and re-enter the cell cycle when prompted by appropriate signals. Using a budding yeast model of cellular quiescence, we investigated the program that initiated DNA replication when these G0 cells resumed growth. Read More

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January 2021