Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Diverse digital and fuzzy composite transcriptional elements are prevalent features of mammalian cis-regulomes

View ORCID ProfileVirendra K. Chaudhri, Harinder Singh
doi: https://doi.org/10.1101/2021.11.26.470154
Virendra K. Chaudhri
1Center for Systems Immunology and Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Virendra K. Chaudhri
  • For correspondence: virendra.chaudhri@pitt.edu harinder@pitt.edu
Harinder Singh
1Center for Systems Immunology and Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
2Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: virendra.chaudhri@pitt.edu harinder@pitt.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

Mammalian transcriptional regulatory sequences are comprised of complex combinations of simple transcription factor (TF) motifs. Stereospecific juxta-positioning of simple TF motifs generates composite elements (CEs), that increase combinatorial and regulatory specificity of TF-DNA interactions. Although a small number of CEs and their cooperative or anti-cooperative modes of TF binding have been thoroughly characterized, a systematic analysis of CE diversity, prevalence and properties in cis-regulomes has not been undertaken. We developed a computational pipeline termed CEseek to discover >20,000 CEs in open chromatin regions of diverse immune cells and validated many using CAP-SELEX, ChIP-Seq and STARR-seq datasets. Strikingly, the CEs manifested a bimodal distribution of configurations, termed digital and fuzzy, based on their stringent or relaxed stereospecific constraints, respectively. Digital CEs mediate cooperative as well as anti-cooperative binding of structurally diverse TFs that likely reflect AND/OR genomic logic gates. In contrast, fuzzy CEs encompass a less diverse set of TF motif pairs that are selectively enriched in p300 associated, multi-genic enhancers. The annotated CEs greatly expand the regulatory DNA motif lexicon and the universe of TF-TF interactions that underlie combinatorial logic of gene regulation.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/viren-v/CEseek

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted November 27, 2021.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Diverse digital and fuzzy composite transcriptional elements are prevalent features of mammalian cis-regulomes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Diverse digital and fuzzy composite transcriptional elements are prevalent features of mammalian cis-regulomes
Virendra K. Chaudhri, Harinder Singh
bioRxiv 2021.11.26.470154; doi: https://doi.org/10.1101/2021.11.26.470154
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Diverse digital and fuzzy composite transcriptional elements are prevalent features of mammalian cis-regulomes
Virendra K. Chaudhri, Harinder Singh
bioRxiv 2021.11.26.470154; doi: https://doi.org/10.1101/2021.11.26.470154

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4381)
  • Biochemistry (9581)
  • Bioengineering (7086)
  • Bioinformatics (24844)
  • Biophysics (12597)
  • Cancer Biology (9952)
  • Cell Biology (14345)
  • Clinical Trials (138)
  • Developmental Biology (7944)
  • Ecology (12101)
  • Epidemiology (2067)
  • Evolutionary Biology (15984)
  • Genetics (10921)
  • Genomics (14735)
  • Immunology (9869)
  • Microbiology (23645)
  • Molecular Biology (9477)
  • Neuroscience (50838)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2681)
  • Physiology (4013)
  • Plant Biology (8655)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2391)
  • Systems Biology (6427)
  • Zoology (1346)