Your browser doesn't support javascript.
loading
Activity-dependent regulome of human GABAergic neurons reveals new patterns of gene regulation and neurological disease heritability.
Boulting, Gabriella L; Durresi, Ershela; Ataman, Bulent; Sherman, Maxwell A; Mei, Kevin; Harmin, David A; Carter, Ava C; Hochbaum, Daniel R; Granger, Adam J; Engreitz, Jesse M; Hrvatin, Sinisa; Blanchard, Michael R; Yang, Marty G; Griffith, Eric C; Greenberg, Michael E.
Affiliation
  • Boulting GL; Department of Neurobiology, Harvard Medical School, Boston, MA, USA. gabriella_boulting@hms.harvard.edu.
  • Durresi E; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Ataman B; MD-PhD Program, Harvard Medical School, Boston, MA, USA.
  • Sherman MA; Department of Internal Medicine, NYU Langone Medical Center and NYU School of Medicine, New York, NY, USA.
  • Mei K; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Harmin DA; Division of Genetics & Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
  • Carter AC; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Hochbaum DR; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Granger AJ; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Engreitz JM; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Hrvatin S; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Blanchard MR; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Yang MG; Department of Genetics, Stanford University School of Medicine and BASE Initiative, Betty Irene Moore Children's Heart Center, Lucile Packard Children's Hospital, Stanford, CA, USA.
  • Griffith EC; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Greenberg ME; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Nat Neurosci ; 24(3): 437-448, 2021 03.
Article in En | MEDLINE | ID: mdl-33542524
Neuronal activity-dependent gene expression is essential for brain development. Although transcriptional and epigenetic effects of neuronal activity have been explored in mice, such an investigation is lacking in humans. Because alterations in GABAergic neuronal circuits are implicated in neurological disorders, we conducted a comprehensive activity-dependent transcriptional and epigenetic profiling of human induced pluripotent stem cell-derived GABAergic neurons similar to those of the early developing striatum. We identified genes whose expression is inducible after membrane depolarization, some of which have specifically evolved in primates and/or are associated with neurological diseases, including schizophrenia and autism spectrum disorder (ASD). We define the genome-wide profile of human neuronal activity-dependent enhancers, promoters and the transcription factors CREB and CRTC1. We found significant heritability enrichment for ASD in the inducible promoters. Our results suggest that sequence variation within activity-inducible promoters of developing human forebrain GABAergic neurons contributes to ASD risk.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Gene Expression Regulation / Epigenesis, Genetic / GABAergic Neurons Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country: Estados Unidos Country of publication: Estados Unidos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Gene Expression Regulation / Epigenesis, Genetic / GABAergic Neurons Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country: Estados Unidos Country of publication: Estados Unidos