Identifying chromatin features that regulate gene expression distribution

Abstract Gene expression variability, differences in the number of mRNA per cell across a population of cells, is ubiquitous across diverse organisms with broad impacts on cellular phenotypes. The role of chromatin in regulating average gene expression has been extensively studied. However, what asp...

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Autores principales: Thanutra Zhang, Robert Foreman, Roy Wollman
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/83e4bca66a19494ab91ec682b35b09aa
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spelling oai:doaj.org-article:83e4bca66a19494ab91ec682b35b09aa2021-12-02T12:33:54ZIdentifying chromatin features that regulate gene expression distribution10.1038/s41598-020-77638-22045-2322https://doaj.org/article/83e4bca66a19494ab91ec682b35b09aa2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77638-2https://doaj.org/toc/2045-2322Abstract Gene expression variability, differences in the number of mRNA per cell across a population of cells, is ubiquitous across diverse organisms with broad impacts on cellular phenotypes. The role of chromatin in regulating average gene expression has been extensively studied. However, what aspects of the chromatin contribute to gene expression variability is still underexplored. Here we addressed this problem by leveraging chromatin diversity and using a systematic investigation of randomly integrated expression reporters to identify what aspects of chromatin microenvironment contribute to gene expression variability. Using DNA barcoding and split-pool decoding, we created a large library of isogenic reporter clones and identified reporter integration sites in a massive and parallel manner. By mapping our measurements of reporter expression at different genomic loci with multiple epigenetic profiles including the enrichment of transcription factors and the distance to different chromatin states, we identified new factors that impact the regulation of gene expression distributions.Thanutra ZhangRobert ForemanRoy WollmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Thanutra Zhang
Robert Foreman
Roy Wollman
Identifying chromatin features that regulate gene expression distribution
description Abstract Gene expression variability, differences in the number of mRNA per cell across a population of cells, is ubiquitous across diverse organisms with broad impacts on cellular phenotypes. The role of chromatin in regulating average gene expression has been extensively studied. However, what aspects of the chromatin contribute to gene expression variability is still underexplored. Here we addressed this problem by leveraging chromatin diversity and using a systematic investigation of randomly integrated expression reporters to identify what aspects of chromatin microenvironment contribute to gene expression variability. Using DNA barcoding and split-pool decoding, we created a large library of isogenic reporter clones and identified reporter integration sites in a massive and parallel manner. By mapping our measurements of reporter expression at different genomic loci with multiple epigenetic profiles including the enrichment of transcription factors and the distance to different chromatin states, we identified new factors that impact the regulation of gene expression distributions.
format article
author Thanutra Zhang
Robert Foreman
Roy Wollman
author_facet Thanutra Zhang
Robert Foreman
Roy Wollman
author_sort Thanutra Zhang
title Identifying chromatin features that regulate gene expression distribution
title_short Identifying chromatin features that regulate gene expression distribution
title_full Identifying chromatin features that regulate gene expression distribution
title_fullStr Identifying chromatin features that regulate gene expression distribution
title_full_unstemmed Identifying chromatin features that regulate gene expression distribution
title_sort identifying chromatin features that regulate gene expression distribution
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/83e4bca66a19494ab91ec682b35b09aa
work_keys_str_mv AT thanutrazhang identifyingchromatinfeaturesthatregulategeneexpressiondistribution
AT robertforeman identifyingchromatinfeaturesthatregulategeneexpressiondistribution
AT roywollman identifyingchromatinfeaturesthatregulategeneexpressiondistribution
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