Chromatin remodelers: We are the drivers!!

Tyagi, Monica; Imam, Nasir; Verma, Kirtika; Patel, Ashok Kumar

doi:10.1080/19491034.2016.1211217

Cited by 128 publications

(102 citation statements)

References 124 publications

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“…These enzymes identify patterns of posttranslational modifications on histone tails (acetylation, phosphorylation, methylation, etc.) and DNA, while initiating a complex series of events involving binding of DNA, recruiting cofactors, sliding and/or ejecting of nucleosomes resulting in the compaction of DNA to inhibit gene accessibility, or the opening of chromatin regions to facilitate rapid gene transcription . Of the several families of chromatin remodeling epigenetic enzymes, the SWI/SNF family plays a critical role regulating ATP‐dependent chromatin remodeling in response to hormone stimulation and during cellular reprograming .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

et al. 2018

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Epigenetic enzymes regulate higher-order chromatin architecture and cell-type specific gene expression. The ATPase BRG1 and the SWI/SNF chromatin remodeling complex are epigenetic enzymes that regulate chromatin accessibility during steady and transitional cell states. Experiments in mice show that the loss of BRG1 inhibits cellular reprogramming, while studies using human cells demonstrate that the overexpression of BRG1 enhances reprogramming. We hypothesized that the variation of SWI/SNF subunit expression in the human population would contribute to variability in the efficiency of induced pluripotent stem cells (iPSC) reprogramming. To examine the impact of an individual's sex, ancestry, and age on iPSC reprogramming, we created a novel sex and ancestry balanced cohort of 240 iPSC lines derived from human dermal fibroblasts (DF) from 80 heathy donors. We methodically assessed the reprogramming efficiency of each DF line and then quantified the individual and demographic-specific variations in SWI/SNF chromatin remodeling proteins and mRNA expression. We identified BRG1, BAF155, and BAF60a expression as strongly correlating with iPSC reprogramming efficiency. Additionally, we discovered that high efficiency iPSC reprograming is negatively correlated with donor age, positively correlated with African American descent, and uncorrelated with donor sex. These results show the variations in chromatin remodeling protein expression have a strong impact on iPSC reprogramming. Additionally, our cohort is unique in its large size, diversity, and focus on healthy donors. Consequently, this cohort can be a vital tool for researchers seeking to validate observational results from human population studies and perform detailed mechanistic studies in a controlled cell culture environment. Stem Cells 2018;36:1697-1708.

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Section: Introductionmentioning

confidence: 99%

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

et al. 2018

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“…17 Additional epigenetic-therapeutic strategies, have been based on the functional activity of the dynamic structure of chromatin, but centered on the enzymatic capacity of energy-dependent protein complexes leading to covalent post-translational modifications on the nucleosome, modulating several cellular processes, such as transcription, gene expression, as well as DNA recombination, replication and DNA damage repairing. 22,23 In this regard, some investigations have been conducted, using azacitidine (30-40 mg/m 2 /d) plus Entinostat (7 mg on days 3 and 10, each 28-day cycle) in phase I-II clinical trials with NSCLC patients. 24 On these studies, genepromoter hypermethylation status has been proposed as a quantitative negative prognostic factor (P < 0.001), based on the quantifiable DNA-Methylation on driver gene-promoter sequences, as APC, RASSF1A, CDH13, and CDKN2A in stage I and III NSCLC patients.…”

Section: Epigenetics Therapeutics In Nsclcmentioning

confidence: 99%

Epigenetics in non-small cell lung carcinomas

Peralta‐Arrieta¹,

Armas-López²,

Zúñiga

et al. 2019

Salud Publica Mex

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Objective. To perform a systematic review of the main epigenetic aberrations involved in non-small cell lung carcinomas’ (NSCLC) diagnosis, progression, and therapeutics. Materials and methods. We performed a systematic review of the scientific literature on lung cancer epigenetics, focusing on NSCLC. Results. Several advances in the molecular study of classical epigenetic mechanisms and massive studies of lung cancer epigenome have contributed relevant new evidence revealing that various molecular complexes are functionally influencing genetic-epigenetic and transcriptional mechanisms that promote lung tumorigenesis (initiation, promotion, and progression), and are also involved in NSCLC therapy-resistance mechanisms. Conclusion. Several epigenetic complexes and mechanisms must be analyzed and considered for the design of new and efficient therapies, which could be fundamental to develop an integrated knowledge to achieve a comprehensive lung cancer personalized medicine.

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“…The mammalian SWI/SNF (SWItch/Sucrose Non-Fermentable; mSWI/SNF) complexes belong to a family of chromatin-remodeling enzymes that utilize ATP to modify chromatin structure and DNA/histone contacts [1][2][3]. These chromatin remodelers can either promote or inhibit the accessibility of various factors that control gene transcription, replication, recombination, and repair [4][5][6]. The enzymatic activity of the mSWI/SNF complexes are driven by the ATPase Brahma-related gene 1 (Brg1) or Brahma (Brm) [2,[7][8][9].…”

Section: Introductionmentioning

confidence: 99%

CK2-dependent phosphorylation of the Brg1 chromatin remodeling enzyme occurs during mitosis

Padilla‐Benavides

Haokip

Yoon

et al. 2019

Preprint

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Brg1 (Brahma related gene 1) is one of two mutually exclusive ATPases that can act as the catalytic subunit of mammalian SWI/SNF chromatin remodeling enzymes that facilitate utilization of the DNA in eukaryotic cells. Brg1 is a phospho-protein and its activity is regulated by specific kinases and phosphatases. Previously, we showed that Brg1 interacts with and is phosphorylated by casein kinase 2 (CK2) in a manner that regulates myoblast proliferation.Here we demonstrate that the Brg1-CK2 interaction occurred during mitosis in embryonic somites and in primary myoblasts derived from satellite cells isolated from muscle tissue. The interaction of CK2 activity with Brg1 and the incorporation of a number of other subunits into the mSWI/SNF enzyme complex were independent of CK2 enzymatic activity. CK2-mediated hyperphosphorylation of Brg1 was observed in mitotic cells derived from multiple cell types and organisms, suggesting functional conservation across tissues and species. The mitotically hyperphosphorylated form of Brg1 was localized with soluble chromatin, demonstrating that CK2-mediated phosphorylation of Brg1 is associated with specific partitioning of Brg1 within sub-cellular compartments. Thus CK2 acts a mitotic kinase that regulates Brg1 phosphorylation and sub-cellular localization.function of Brg1 and leads to a block of myogenic differentiation [16]. However, dephosphorylation of Brg1 by the phosphatase, calcineurin, opposes the activity of PKCβ1, allowing chromatin remodeling by Brg1 and initiation of myogenesis [16]. Mutagenesis and unbiased mass spectrometry analyses of Brg1 phosphopeptides in the presence and absence of a calcineurin inhibitor identified calcineurin target sequences, but the mass spectrometry data identified additional Brg1 phosphopeptides that were not responsive to calcineurin inhibition [16]. This suggested that Brg1 is a target of additional signal transduction pathways. Our subsequent studies showed that Brg1 was phosphorylated by casein kinase 2 (CK2), a Serine/Threonine kinase, which promoted myoblast proliferation and survival by regulating subnuclear localization and incorporation of one of two related subunits, BAF155/BAF170, into the enzyme complex [17].CK2 is ubiquitously expressed and functions as a tetramer of two catalytic subunits, CK2α or CK2α', and two CK2β regulatory subunits, and it has more than 300 known substrates [29][30][31].CK2 is required for cell cycle progression, survival, apoptosis, and transcriptional regulation.Knockout mice lacking the CK2α subunit show cardiac and neural tube defects and die during embryogenesis, whereas mice lacking the α' subunit have impaired spermatogenesis [32][33][34].Knockout of the CK2β subunit in mice leads to reduced proliferation during embryogenesis, which is reflected in the small size of the animals at embryonic day 6.5 (E6.5) and resorption at E7.5 [35]. Analyses of a murine conditional knockout model showed that CK2β is essential for viability of embryonic stem cells and primary embryonic fibroblasts [35]. In vitro ...

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Chromatin remodelers: We are the drivers!!

Cited by 128 publications

References 124 publications

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

Epigenetics in non-small cell lung carcinomas

CK2-dependent phosphorylation of the Brg1 chromatin remodeling enzyme occurs during mitosis

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