University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Bioinformatics and Integrative Biology; Graduate School of Biomedical Sciences

Publication Date

2021-06-04

Document Type

Article

Disciplines

Bioinformatics | Computational Biology | Genomics | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

Gene expression is controlled by regulatory elements within accessible chromatin. Although most regulatory elements are cell type-specific, a subset is accessible in nearly all the 517 human and 94 mouse cell and tissue types assayed by the ENCODE consortium. We systematically analyzed 9000 human and 8000 mouse ubiquitously-accessible candidate cis-regulatory elements (cCREs) with promoter-like signatures (PLSs) from ENCODE, which we denote ubi-PLSs. These are more CpG-rich than non-ubi-PLSs and correspond to genes with ubiquitously high transcription, including a majority of cell-essential genes. ubi-PLSs are enriched with motifs of ubiquitously-expressed transcription factors and preferentially bound by transcriptional cofactors regulating ubiquitously-expressed genes. They are highly conserved between human and mouse at the synteny level but exhibit frequent turnover of motif sites; accordingly, ubi-PLSs show increased variation at their centers compared with flanking regions among the approximately 186 thousand human genomes sequenced by the TOPMed project. Finally, ubi-PLSs are enriched in genes implicated in Mendelian diseases, especially diseases broadly impacting most cell types, such as deficiencies in mitochondrial functions. Thus, a set of roughly 9000 mammalian promoters are actively maintained in an accessible state across cell types by a distinct set of transcription factors and cofactors to ensure the transcriptional programs of cell-essential genes.

Keywords

genomics, ENCODE, cis-regulatory elements, cCREs, promoters

Rights and Permissions

Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version

10.1093/nar/gkab345

Source

Fan K, Moore JE, Zhang XO, Weng Z. Genetic and epigenetic features of promoters with ubiquitous chromatin accessibility support ubiquitous transcription of cell-essential genes. Nucleic Acids Res. 2021 Jun 4;49(10):5705-5725. doi: 10.1093/nar/gkab345. PMID: 33978759; PMCID: PMC8191798. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Nucleic acids research

PubMed ID

33978759

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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