Single chromatin fiber profiling and nucleosome position mapping in the human brain.

Autor:	Peter CJ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Agarwal A; Tisch Cancer Institute Bioinformatics for Next Generation Sequencing (BiNGS) Core, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Watanabe R; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute Bioinformatics for Next Generation Sequencing (BiNGS) Core, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Kassim BS; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Wang X; Tisch Cancer Institute Bioinformatics for Next Generation Sequencing (BiNGS) Core, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Lambert TY; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Javidfar B; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Evans V; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Dawson T; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Fridrikh M; Department of Genetics and Genomic Sciences, Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Girdhar K; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Roussos P; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Illness Research Education and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY 10468, USA; Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Bronx, NY 10468, USA., Nageshwaran SK; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA., Tsankova NM; Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Sebra RP; Department of Genetics and Genomic Sciences, Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Vollger MR; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Stergachis AB; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA., Hasson D; Tisch Cancer Institute Bioinformatics for Next Generation Sequencing (BiNGS) Core, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Akbarian S; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: schahram.akbarian@mssm.edu.
Jazyk:	angličtina
Zdroj:	Cell reports methods [Cell Rep Methods] 2024 Nov 25, pp. 100911. Date of Electronic Publication: 2024 Nov 25.
DOI:	10.1016/j.crmeth.2024.100911
Abstrakt:	We apply a single-molecule chromatin fiber sequencing (Fiber-seq) protocol designed for amplification-free cell-type-specific mapping of the regulatory architecture at nucleosome resolution along extended ∼10-kb chromatin fibers to neuronal and non-neuronal nuclei sorted from human brain tissue. Specifically, application of this method enables the resolution of cell-selective promoter and enhancer architectures on single fibers, including transcription factor footprinting and position mapping, with sequence-specific fixation of nucleosome arrays flanking transcription start sites and regulatory motifs. We uncover haplotype-specific chromatin patterns, multiple regulatory elements cis-aligned on individual fibers, and accessible chromatin at 20,000 unique sites encompassing retrotransposons and other repeat sequences hitherto "unmappable" by short-read epigenomic sequencing. Overall, we show that Fiber-seq is applicable to human brain tissue, offering sharp demarcation of nucleosome-depleted regions at sites of open chromatin in conjunction with multi-kilobase nucleosomal positioning at single-fiber resolution on a genome-wide scale. Competing Interests: Declaration of interests A.B.S. is a co-inventor on a patent relating to the Fiber-seq method (US17/995,058). (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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