scholarly journals The INO80 Chromatin Remodeler Sustains Metabolic Stability by Promoting TOR Signaling and Regulating Histone Acetylation

2017 ◽  
Author(s):  
Sean L. Beckwith ◽  
Erin K. Schwartz ◽  
Pablo E. Garcia-Nieto ◽  
Devin A. King ◽  
Graeme J. Gowans ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Chromatin Remodeling ◽  
Cell Function ◽  
Metabolic Stability ◽  
Central Component ◽  
Metabolic Homeostasis ◽  
Tor Signaling ◽  
Chromatin Remodelers ◽  
Chromatin Remodeling Complexes ◽  
Metabolic Regulators

ABSTRACTChromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct functional subunit modules. We identified a strikingly divergent genetic signature for the Ies6 subunit module that links the INO80 complex to metabolic homeostasis, including mitochondrial maintenance. INO80 is also needed to communicate TORC1-mediated signaling to chromatin and maintains histone acetylation at TORC1-responsive genes. Furthermore, computational analysis reveals subunits of INO80 and mTORC1 have high co-occurrence of alterations in human cancers. Collectively, these results demonstrate that the INO80 complex is a central component of metabolic homeostasis that influences histone acetylation and may contribute to disease when disrupted.

Co-dependent recruitment of Ino80p and Snf2p is required for yeast CUP1 activation

2014 ◽  
Vol 92 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Roshini N. Wimalarathna ◽  
Po Yun Pan ◽  
Chang-Hui Shen
Keyword(s):  
Rna Polymerase ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Transcriptional Activation ◽  
Copper Toxicity ◽  
Yeast Cells ◽  
Chromatin Remodelers ◽  
Insight Into ◽  
Cup1 Promoter

In yeast, Ace1p-dependent induction of CUP1 is responsible for protecting cells from copper toxicity. Although the mechanism of yeast CUP1 induction has been studied intensively, it is still uncertain which chromatin remodelers are involved in CUP1 transcriptional activation. Here, we show that yeast cells are inviable in the presence of copper when either chromatin remodeler, Ino80p or Snf2p, is not present. This inviability is due to the lack of CUP1 expression in ino80Δ and snf2Δ cells. Subsequently, we observe that both Ino80p and Snf2p are present at the promoter and they are responsible for recruiting chromatin remodeling activity to the CUP1 promoter under induced conditions. These results suggest that they directly participate in CUP1 transcriptional activation. Furthermore, the codependent recruitment of both INO80 and SWI/SNF depends on the presence of the transcriptional activator, Ace1p. We also demonstrate that both remodelers are required to recruit RNA polymerase II and targeted histone acetylation, indicating that remodelers are recruited to the CUP1 promoter before RNA polymerase II and histone acetylases. These observations provide evidence for the mechanism of CUP1 induction. As such, we propose a model that describes novel insight into the order of events in CUP1 activation.

scholarly journals The Emerging Role of ATP-Dependent Chromatin Remodeling in Memory and Substance Use Disorders

2020 ◽  
Vol 21 (18) ◽  
pp. 6816
Author(s):  
Alberto J. López ◽  
Julia K. Hecking ◽  
André O. White
Keyword(s):  
Gene Expression ◽  
Substance Use ◽  
Substance Use Disorders ◽  
Chromatin Remodeling ◽  
Cell Function ◽  
Regulation Of Gene Expression ◽  
Memory Formation ◽  
Epigenetic Mechanism ◽  
Chromatin Remodelers ◽  
Histone Modifying Enzymes

Long-term memory formation requires coordinated regulation of gene expression and persistent changes in cell function. For decades, research has implicated histone modifications in regulating chromatin compaction necessary for experience-dependent changes to gene expression and cell function during memory formation. Recent evidence suggests that another epigenetic mechanism, ATP-dependent chromatin remodeling, works in concert with the histone-modifying enzymes to produce large-scale changes to chromatin structure. This review examines how histone-modifying enzymes and chromatin remodelers restructure chromatin to facilitate memory formation. We highlight the emerging evidence implicating ATP-dependent chromatin remodeling as an essential mechanism that mediates activity-dependent gene expression, plasticity, and cell function in developing and adult brains. Finally, we discuss how studies that target chromatin remodelers have expanded our understanding of the role that these complexes play in substance use disorders.

scholarly journals GBAF, a small BAF sub-complex with big implications: a systematic review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sarah M. Innis ◽  
Birgit Cabot
Keyword(s):  
Chromatin Remodeling ◽  
Cellular Differentiation ◽  
Complex Function ◽  
Therapeutic Interventions ◽  
Mammalian Development ◽  
Aberrant Expression ◽  
Chromatin Remodelers ◽  
Baf Complex ◽  
Chromatin Remodeling Complexes ◽  
Histone Modifying Enzymes

Abstract ATP-dependent chromatin remodeling by histone-modifying enzymes and chromatin remodeling complexes is crucial for maintaining chromatin organization and facilitating gene transcription. In the SWI/SNF family of ATP-dependent chromatin remodelers, distinct complexes such as BAF, PBAF, GBAF, esBAF and npBAF/nBAF are of particular interest regarding their implications in cellular differentiation and development, as well as in various diseases. The recently identified BAF subcomplex GBAF is no exception to this, and information is emerging linking this complex and its components to crucial events in mammalian development. Furthermore, given the essential nature of many of its subunits in maintaining effective chromatin remodeling function, it comes as no surprise that aberrant expression of GBAF complex components is associated with disease development, including neurodevelopmental disorders and numerous malignancies. It becomes clear that building upon our knowledge of GBAF and BAF complex function will be essential for advancements in both mammalian reproductive applications and the development of more effective therapeutic interventions and strategies. Here, we review the roles of the SWI/SNF chromatin remodeling subcomplex GBAF and its subunits in mammalian development and disease.

scholarly journals Characterizing the role of SWI/SNF-related chromatin remodeling complexes in planarian regeneration and stem cell function

2018 ◽  
Vol 32 ◽  
pp. 91-103 ◽  
Author(s):  
Toria Trost ◽  
Jessica Haines ◽  
Austin Dillon ◽  
Brittany Mersman ◽  
Mallory Robbins ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chromatin Remodeling ◽  
Cell Function ◽  
Planarian Regeneration ◽  
Chromatin Remodeling Complexes

Functional diversity of ISWI complexes

2004 ◽  
Vol 82 (4) ◽  
pp. 482-489 ◽  
Author(s):  
Sara S Dirscherl ◽  
Jocelyn E Krebs
Keyword(s):  
Chromatin Remodeling ◽  
Catalytic Core ◽  
Chromatin Remodelers ◽  
Form And Function ◽  
Curr Opin Cell Biol ◽  
Chromatid Cohesion ◽  
Chromatin Remodeling Complexes ◽  
And Function ◽  
Diverse Groups ◽  
Nuclear Processes

The yeast SWI/SNF ATP-dependent chromatin remodeling complex was first identified and characterized over 10 years ago (F. Winston and M. Carlson. 1992. Trends Genet. 8: 387–391.) Since then, the number of distinct ATP-dependent chromatin remodeling complexes and the variety of roles they play in nuclear processes have become dizzying (J.A. Martens and F. Winston. 2003. Curr. Opin. Genet. Dev. 13: 136–142; A. Vacquero et al. 2003. Sci. Aging Knowledge Environ. 2003: RE4) — and that does not even include the companion suite of histone modifying enzymes, which exhibit a comparable diversity in both number of complexes and variety of functions (M.J. Carrozza et al. 2003. Trends Genet. 19: 321–329; W. Fischle et al. 2003. Curr. Opin. Cell Biol. 15: 172–183; M. Iizuka and M.M. Smith. 2003. Curr. Opin. Genet. Dev. 13: 1529–1539). This vast complexity is hardly surprising, given that all nuclear processes that involve DNA — transcription, replication, repair, recombination, sister chromatid cohesion, etc. — must all occur in the context of chromatin. The SWI/SNF-related ATP-dependent remodelers are divided into a number of subfamilies, all related by the SWI2/SNF2 ATPase at their catalytic core. In nearly every species where researchers have looked for them, one or more members of each subfamily have been identified. Even the budding yeast, with its comparatively small genome, contains eight different chromatin remodelers in five different subfamilies. This review will focus on just one subfamily, the Imitation Switch (ISWI) family, which is proving to be one of the most diverse groups of chromatin remodelers in both form and function.

scholarly journals The INO80 chromatin remodeler sustains metabolic stability by promoting TOR signaling and regulating histone acetylation

PLoS Genetics ◽  
2018 ◽  
Vol 14 (2) ◽  
pp. e1007216 ◽  
Author(s):  
Sean L. Beckwith ◽  
Erin K. Schwartz ◽  
Pablo E. García-Nieto ◽  
Devin A. King ◽  
Graeme J. Gowans ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Metabolic Stability ◽  
Chromatin Remodeler ◽  
Tor Signaling

scholarly journals The BAF53a subunit of SWI/SNF-like BAF complexes is essential for hemopoietic stem cell function

Blood ◽  
2012 ◽  
Vol 120 (24) ◽  
pp. 4720-4732 ◽  
Author(s):  
Veneta Krasteva ◽  
Manuel Buscarlet ◽  
Abigail Diaz-Tellez ◽  
Marie-Anne Bernard ◽  
Gerald R. Crabtree ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chromatin Remodeling ◽  
Progenitor Cell ◽  
Cell Function ◽  
Adult Stem Cell ◽  
Hemopoietic Stem Cell ◽  
Conditional Deletion ◽  
Chromatin Remodeling Complexes ◽  
A Subunit

Abstract ATP-dependent SWI/SNF-like BAF chromatin remodeling complexes are emerging as key regulators of embryonic and adult stem cell function. Particularly intriguing are the findings that specialized assemblies of BAF complexes are required for establishing and maintaining pluripotent and multipotent states in cells. However, little is known on the importance of these complexes in normal and leukemic hemopoiesis. Here we provide the first evidence that the actin-related protein BAF53a, a subunit of BAF complexes preferentially expressed in long-term repopulating stem cells, is essential for adult hemopoiesis. Conditional deletion of BAF53a resulted in multilineage BM failure, aplastic anemia, and rapid lethality. These severe hemopoietic defects originate from a proliferative impairment of BM HSCs and progenitors and decreased progenitor survival. Using hemopoietic chimeras, we show that the impaired function of BAF53a-deficient HSCs is cell-autonomous and independent of the BM microenvironment. Altogether, our studies highlight an unsuspected role for BAF chromatin remodeling complexes in the maintenance of HSC and progenitor cell properties.

scholarly journals Transcriptional Profiling of Cardiac Cells Links Age-Dependent Changes in Acetyl-CoA Signaling to Chromatin Modifications

2021 ◽  
Vol 22 (13) ◽  
pp. 6987
Author(s):  
Justin Kurian ◽  
Veronica Bohl ◽  
Michael Behanan ◽  
Sadia Mohsin ◽  
Mohsin Khan
Keyword(s):  
Histone Acetylation ◽  
Chromatin Remodeling ◽  
Cardiac Tissue ◽  
Transcriptional Profiling ◽  
Cardiac Cells ◽  
Fine Tuning ◽  
Rna Seq ◽  
Acetyl Coa ◽  
Metabolic Regulators ◽  
Multilineage Potential

Metabolism has emerged as a regulator of core stem cell properties such as proliferation, survival, self-renewal, and multilineage potential. Metabolites serve as secondary messengers, fine-tuning signaling pathways in response to microenvironment alterations. Studies show a role for central metabolite acetyl-CoA in the regulation of chromatin state through changes in histone acetylation. Nevertheless, metabolic regulators of chromatin remodeling in cardiac cells in response to increasing biological age remains unknown. Previously, we identified novel cardiac-derived stem-like cells (CTSCs) that exhibit increased functional properties in the neonatal heart (nCTSC). These cells are linked to a unique metabolism which is altered with CTSC aging (aCTSC). Here, we present an in-depth, RNA-sequencing-based (RNA-Seq) bioinformatic with cluster analysis that details a distinct epigenome present in nCTSCs but not in aCTSCs. Gene Ontology (GO) and pathway enrichment reveal biological processes, including metabolism, gene regulation enriched in nCTSCs, and STRING analysis that identifies a network of genes related to acetyl-CoA that can potentially influence chromatin remodeling. Additional validation by Western blot and qRT-PCR shows increased acetyl-CoA signaling and histone acetylation in nCTSCs compared to aCTSCs. In conclusion, our data reveal that the link between metabolism and histone acetylation in cardiac cells is altered with the aging of the cardiac tissue.

How many remodelers does it take to make a brain? Diverse and cooperative roles of ATP-dependent chromatin-remodeling complexes in developmentThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2007 ◽  
Vol 85 (4) ◽  
pp. 444-462 ◽  
Author(s):  
Elvin Brown ◽  
Sreepurna Malakar ◽  
Jocelyn E. Krebs
Keyword(s):  
Chromatin Remodeling ◽  
Dna Sequences ◽  
Protein Complexes ◽  
Peer Review Process ◽  
Chromatin Remodelers ◽  
Dna Accessibility ◽  
Stage Of Development ◽  
Chromatin Remodeling Complexes ◽  
Cellular Machinery ◽  
Selection Of

The development of a metazoan from a single-celled zygote to a complex multicellular organism requires elaborate and carefully regulated programs of gene expression. However, the tight packaging of genomic DNA into chromatin makes genes inaccessible to the cellular machinery and must be overcome by the processes of chromatin remodeling; in addition, chromatin remodeling can preferentially silence genes when their expression is not required. One class of chromatin remodelers, ATP-dependent chromatin-remodeling enzymes, can slide nucleosomes along the DNA to make specific DNA sequences accessible or inaccessible to regulators at a particular stage of development. While all ATPases in the SWI2/SNF2 superfamily share the fundamental ability to alter DNA accessibility in chromatin, they do not act alone, but rather, are subunits of a large assortment of protein complexes. Recent studies illuminate common themes by which the subunit compositions of chromatin-remodeling complexes specify the developmental roles that chromatin remodelers play in specific tissues and at specific stages of development, in response to specific signaling pathways and transcription factors. In this review, we will discuss the known roles in metazoan development of 3 major subfamilies of chromatin-remodeling complexes: the SNF2, ISWI, and CHD subfamilies.

scholarly journals ATP-Dependent Chromatin Remodeling Complex in the Lineage Specification of Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Wen Du ◽  
Daimo Guo ◽  
Wei Du
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chromatin Remodeling ◽  
Cardiac Tissue ◽  
Gene Expression Regulation ◽  
Atp Hydrolysis ◽  
Transcriptional Level ◽  
Lineage Specification ◽  
Chromatin Remodelers ◽  
Chromatin Remodeling Complexes

Mesenchymal stem cells (MSCs) present in multiple tissues can self-renew and differentiate into multiple lineages including the bone, cartilage, muscle, cardiac tissue, and connective tissue. Key events, including cell proliferation, lineage commitment, and MSC differentiation, are ensured by precise gene expression regulation. ATP-dependent chromatin alteration is one form of epigenetic modifications that can regulate the transcriptional level of specific genes by utilizing the energy from ATP hydrolysis to reorganize chromatin structure. ATP-dependent chromatin remodeling complexes consist of a variety of subunits that together perform multiple functions in self-renewal and lineage specification. This review highlights the important role of ATP-dependent chromatin remodeling complexes and their different subunits in modulating MSC fate determination and discusses the proposed mechanisms by which ATP-dependent chromatin remodelers function.

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