Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling complexes modulates Pdx1 activity in islet β cells.

Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet β cell function. However, little is known about the positive- and negative-acting coregulators recruited to mediate transcriptional control. Here, we isolated numerous Pdx1-interacting factors possessing a wide range of cellular functions linked with this protein, including, but not limited to, coregulators associated with transcriptional activation and repression, DNA damage response, and DNA replication. Because chromatin remodeling activities are essential to developmental lineage decisions and adult cell function, our analysis focused on investigating the influence of the Swi/Snf chromatin remodeler on Pdx1 action. The two mutually exclusive and indispensable Swi/Snf core ATPase subunits, Brg1 and Brm, distinctly affected target gene expression in β cells. Furthermore, physiological and pathophysiological conditions dynamically regulated Pdx1 binding to these Swi/Snf complexes in vivo. We discuss how context-dependent recruitment of coregulatory complexes by Pdx1 could impact pancreas cell development and adult islet β cell activity.

• Publication year

  2015

• Venue

  Cell Reports

• Publication date

  2015-03-31

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.celrep.2015.02.054PMID 25801033PMCID PMC4651178
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Genome-Wide DNA Methylation Analysis of Human Pancreatic Islets from Type 2 Diabetic and Non-Diabetic Donors Identifies Candidate Genes That Influence Insulin Secretion

  2014cited by this paper
• The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma

  2014cited by this paper
• Pdx1 maintains β cell identity and function by repressing an α cell program.

  2014cited by this paper
• Islet α-, β-, and δ-Cell Development Is Controlled by the Ldb1 Coregulator, Acting Primarily With the Islet-1 Transcription Factor

  2013cited by this paper
• Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants

  2013cited by this paper
• Inactivation of specific β cell transcription factors in type 2 diabetes.

  2013cited by this paper
• Sumoylation: a regulatory protein modification in health and disease.

  2013cited by this paper
• The Mediator complex and transcription regulation

  2013cited by this paper
• Pancreatic islet enhancer clusters enriched in type 2 diabetes risk–associated variants

  2013cited by this paper
• Functional Redundancy of SWI/SNF Catalytic Subunits in Maintaining Vascular Endothelial Cells in the Adult Heart

  2012cited by this paper
• Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: a role for ovarian hormones[S]

  2012cited by this paper
• Combined gene dosage requirement for SWI/SNF catalytic subunits during early mammalian development

  2012cited by this paper
• Functional Analysis of KAP1 Genomic Recruitment

  2011cited by this paper
• Nkx2.2 repressor complex regulates islet β-cell specification and prevents β-to-α-cell reprogramming.

  2011cited by this paper
• Context-specific α- to-β-cell reprogramming by forced Pdx1 expression.

  2011cited by this paper
• Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx.

  2011cited by this paper
• ReCLIP (Reversible Cross-Link Immuno-Precipitation): An Efficient Method for Interrogation of Labile Protein Complexes

  2011cited by this paper
• A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion.

  2011cited by this paper
• NuRD mediates activating and repressive functions of GATA‐1 and FOG‐1 during blood development

  2010cited by this paper
• Phosphorylation within the MafA N Terminus Regulates C-terminal Dimerization and DNA Binding*

  2010cited by this paper
• Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice.

  2010cited by this paper
• Genetic and biochemical pathways of β‐cell failure in type 2 diabetes

  2009cited by this paper
• Antagonistic Roles for BRM and BRG1 SWI/SNF Complexes in Differentiation

  2009cited by this paper
• pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis.

  2008cited by this paper
• Covalent modifications of histones during development and disease pathogenesis

  2007cited by this paper
• A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis.

  2007cited by this paper
• Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver

  2007cited by this paper
• SOX9 is required for maintenance of the pancreatic progenitor cell pool

  2007cited by this paper
• An essential switch in subunit composition of a chromatin remodeling complex during neural development.

  2007cited by this paper
• MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells.

  2006cited by this paper
• Complementation rescue of Pdx1 null phenotype demonstrates distinct roles of proximal and distal cis-regulatory sequences in pancreatic and duodenal expression.

  2006cited by this paper
• MafB: An Activator of the Glucagon Gene Expressed in Developing Islet α- and β-Cells

  2006cited by this paper
• The coactivator Bridge-1 increases transcriptional activation by pancreas duodenum homeobox-1 (PDX-1).

  2005cited by this paper
• Regulation of the Pancreatic Duodenal Homeobox-1 Protein by DNA-dependent Protein Kinase*

  2005cited by this paper
• The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas.

  2005cited by this paper
• The Islet β Cell-enriched MafA Activator Is a Key Regulator of Insulin Gene Transcription*

  2005cited by this paper
• Pdx-1 Links Histone H3-Lys-4 Methylation to RNA Polymerase II Elongation during Activation of Insulin Transcription*

  2005cited by this paper
• HNF1beta/TCF2 mutations impair transactivation potential through altered co-regulator recruitment.

  2004cited by this paper
• Structure and function of eukaryotic DNA methyltransferases.

  2004cited by this paper
• Glucose regulation of insulin gene expression requires the recruitment of p300 by the beta-cell-specific transcription factor Pdx-1.

  2004cited by this paper
• The Pancreatic Duodenal Homeobox-1 Protein (Pdx-1) Interacts with Histone Deacetylases Hdac-1 and Hdac-2 on Low Levels of Glucose*

  2004cited by this paper
• Identification of PCIF1, a POZ Domain Protein That Inhibits PDX-1 (MODY4) Transcriptional Activity

  2004cited by this paper
• Baf60c is essential for function of BAF chromatin remodelling complexes in heart development

  2004cited by this paper
• Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development.

  2003cited by this paper
• O-GlcNAc: a regulatory post-translational modification.

  2003cited by this paper
• Members of the Large Maf Transcription Family Regulate Insulin Gene Transcription in Islet β Cells

  2003cited by this paper
• Insulin Gene Transcription Is Mediated by Interactions between the p300 Coactivator and PDX-1, BETA2, and E47

  2002cited by this paper
• Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding.

  2002cited by this paper
• The Role of Hepatic Nuclear Factor 1α and PDX-1 in Transcriptional Regulation of the pdx-1 Gene*

  2001cited by this paper
• The role of hepatic nuclear factor 1 alpha and PDX-1 in transcriptional regulation of the pdx-1 gene.

  2001cited by this paper
• The Swi/Snf family nucleosome-remodeling complexes and transcriptional control.

  2000cited by this paper
• A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes.

  2000cited by this paper
• Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits.

  1999cited by this paper
• Bridge-1, a Novel PDZ-Domain Coactivator of E2A-Mediated Regulation of Insulin Gene Transcription

  1999cited by this paper
• Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α)

  1998cited by this paper
• p300 Mediates Transcriptional Stimulation by the Basic Helix-Loop-Helix Activators of the Insulin Gene

  1998cited by this paper
• The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas.

  1998cited by this paper
• Homeodomain protein IDX-1: a master regulator of pancreas development and insulin gene expression.

  1997cited by this paper
• PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum.

  1996cited by this paper
• Purification and biochemical heterogeneity of the mammalian SWI‐SNF complex.

  1996cited by this paper
• Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny.

  1995cited by this paper
• Insulin-promoter-factor 1 is required for pancreas development in mice

  1994cited by this paper
• BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription

  1993cited by this paper
• IPF1, a homeodomain‐containing transactivator of the insulin gene.

  1993cited by this paper
• Altered glucose regulation of insulin biosynthesis in insulinoma cells: mouse beta TC3 cells secrete insulin-related peptides predominantly via a constitutive pathway.

  1992cited by this paper
• Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.

  1989cited by this paper

• BAF60a-dependent chromatin remodeling preserves β cell function and contributes to the therapeutic benefits of GLP-1R agonists

  2025cites this paper
• Chromatin sensing: Integration of environmental signals to reprogram plant development through chromatin regulators.

  2024cites this paper
• The SWI/SNF chromatin remodelling complex regulates pancreatic endocrine cell expansion and differentiation in mice in vivo

  2024cites this paper
• Hyperglycemia influences the cell proliferation and death of the rat endocrine pancreas in the neonatal period.

  2024cites this paper
• Ablation of Brg1 in fibroblast/myofibroblast lineages attenuates renal fibrosis in mice with diabetic nephropathy.

  2024cites this paper
• Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis.

  2024cites this paper
• The Chd4 helicase regulates chromatin accessibility and gene expression critical for β-cell function in vivo.

  2023cites this paper
• Dynamic regulation of pancreatic β cell function and gene expression by the SND1 coregulator in vitro

  2023cites this paper
• Transcriptional control of pancreatic β-cell identity and plasticity during the pathogenesis of type 2 diabetes.

  2022cites this paper
• PDX1 is the cornerstone of pancreatic β-cell functions and identity

  2022cites this paper
• Journal Pre-proof insights into glucose-dependent transcriptional regulation by PDX1

  2022influential citation
• Biophysical insights into glucose-dependent transcriptional regulation by PDX1

  2022influential citation
• Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling.

  2022cites this paper
• Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells

  2022cites this paper
• The Ldb1 transcriptional co‐regulator is required for establishment and maintenance of the pancreatic endocrine lineage

  2022cites this paper
• SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression.

  2022cites this paper
• The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function.

  2022cites this paper
• Epigenetic Regulation of β Cell Identity and Dysfunction

  2021cites this paper
• Groucho co-repressor proteins regulate β cell development and proliferation by repressing Foxa1 in the developing mouse pancreas

  2021cites this paper
• Epigenetics, microRNA and Metabolic Syndrome: A Comprehensive Review

  2021cites this paper
• A δ-cell subpopulation with a pro-β-cell identity confers efficient age-independent recovery in a zebrafish model of diabetes

  2021cites this paper
• The Transcriptome and Epigenome Reveal Novel Changes in Transcription Regulation During Pancreatic Rat Islet Maturation.

  2021cites this paper
• LDB1-mediated transcriptional complexes are sensitive to islet stress

  2021cites this paper
• Secretome effect of adipose tissue-derived stem cells cultured two-dimensionally and three-dimensionally in mice with streptozocin induced type 1 diabetes

  2021cites this paper
• Epigenetics in β-cell adaptation and type 2 diabetes.

  2020cites this paper
• The Contribution of Transcriptional Coregulators in the Maintenance of β-cell Function and Identity.

  2020cites this paper
• Pancreas development and the Polycomb group protein complexes.

  2020cites this paper
• Effects and mechanism of stem cells from human exfoliated deciduous teeth combined with hyperbaric oxygen therapy in type 2 diabetic rats

  2020cites this paper
• Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling

  2020cites this paper
• Study of human regulatory mutations associated with pancreatic diseases by humanizing the zebrafish genome.

  2019cites this paper
• Epigenetic Modifications Associated with the Pathogenesis of Type 2 Diabetes Mellitus.

  2019cites this paper
• LIM-domain transcription complexes interact with ring-finger ubiquitin ligases and thereby impact islet β-cell function

  2019cites this paper
• The Pdx1-Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet β-Cell Function

  2019cites this paper
• Epigenetic Mechanisms in Liver and Pancreas Generation and Regeneration

  2019cites this paper
• Epigenetics and Type 2 Diabetes Risk

  2019cites this paper
• Unwinding chromatin at the right places: how BAF is targeted to specific genomic locations during development

  2019cites this paper
• The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

  2019cites this paper
• β-cell dedifferentiation is associated with epithelial-mesenchymal transition triggered by miR-7-mediated repression of mSwi/Snf complex

  2019cites this paper
• Epigenetic Aspects of Nuclear Receptor Coregulators: How Nutritional and Environmental Signals Change Gene Expression Patterns

  2018cites this paper
• The BRG1/SOX9 axis is critical for acinar cell–derived pancreatic tumorigenesis

  2018cites this paper
• Epigenetics of metabolic syndrome.

  2018cites this paper
• Clec16a, Nrdp1, and USP8 Form a Ubiquitin-Dependent Tripartite Complex That Regulates β-Cell Mitophagy

  2017cites this paper
• The mammal-specific Pdx1 Area II enhancer has multiple essential functions in early endocrine cell specification and postnatal β-cell maturation

  2017cites this paper
• Epigenetic control of β-cell function and failure.

  2017cites this paper
• Epigenetics in formation, function, and failure of the endocrine pancreas

  2017cites this paper
• PAX4 promotes PDX1-induced differentiation of mesenchymal stem cells into insulin-secreting cells.

  2017cites this paper
• Etude du rôle de facteurs génétiques et épigénétiques dans l'homéostasie et la fonction des cellules pancréatiques

  2017cites this paper
• LDB1 Regulates Energy Homeostasis During Diet-Induced Obesity

  2017cites this paper
• Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo

  2017cites this paper
• The Role of SWI/SNF Chromatin Remodeling Complexes in Hormone Crosstalk.

  2016cites this paper
• Viruses Implicated in the Initiation of Type 1 Diabetes Affect β Cell Function and Antiviral Innate Immune Responses: A Dissertation

  2016cites this paper
• Impact of Pdx1‐associated chromatin modifiers on islet β‐cells

  2016cites this paper
• β‐cell differentiation status in type 2 diabetes

  2016cites this paper
• The Role of SWI/SNF Chromatin Remodeling Complexes in Hormone

  2016cites this paper
• Alterations of Epigenetic Regulators in Pancreatic Cancer and Their Clinical Implications

  2016cites this paper
• Mass production of functional human pancreatic β‐cells: why and how?

  2016cites this paper
• Chromatin Regulators in Pancreas Development and Diabetes.

  2016cites this paper
• Implication of epigenetics in pancreas development and disease.

  2015cites this paper
• SSBP3 Interacts With Islet-1 and Ldb1 to Impact Pancreatic β-Cell Target Genes.

  2015cites this paper