Nature Communications (Apr 2022)
Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia
- Lorna A. Farrelly,
- Shuangping Zheng,
- Nadine Schrode,
- Aaron Topol,
- Natarajan V. Bhanu,
- Ryan M. Bastle,
- Aarthi Ramakrishnan,
- Jennifer C Chan,
- Bulent Cetin,
- Erin Flaherty,
- Li Shen,
- Kelly Gleason,
- Carol A. Tamminga,
- Benjamin A. Garcia,
- Haitao Li,
- Kristen J. Brennand,
- Ian Maze
Affiliations
- Lorna A. Farrelly
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Shuangping Zheng
- Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Protein Sciences, Department of Basic Medical Sciences, School of Medicine, Tsinghua University
- Nadine Schrode
- Department of Genetics and Genomic Sciences, Pamela Sklar Division of Psychiatric Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai
- Aaron Topol
- Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai
- Natarajan V. Bhanu
- Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania
- Ryan M. Bastle
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Aarthi Ramakrishnan
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Jennifer C Chan
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Bulent Cetin
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Erin Flaherty
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Li Shen
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Kelly Gleason
- Department of Psychiatry, University of Texas Southwestern Medical School
- Carol A. Tamminga
- Department of Psychiatry, University of Texas Southwestern Medical School
- Benjamin A. Garcia
- Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania
- Haitao Li
- Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Protein Sciences, Department of Basic Medical Sciences, School of Medicine, Tsinghua University
- Kristen J. Brennand
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- Ian Maze
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
- DOI
- https://doi.org/10.1038/s41467-022-29922-0
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 10
Abstract
Schizophrenia (SZ) is a severe psychiatric disorder; unfortunately, only ~1/3 of patients respond favorably to treatment. Here, the authors reveal hyperacetylation of histone H2A.Z in SZ neurons and postmortem SZ human brain tissues. They further show BRD4 is a reader of hyperacetylated H2A.Z and treatment with bromodomain inhibitor JQ1 largely rescues abnormal gene expression associated with SZ.
