Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.

Handle URI:
http://hdl.handle.net/10754/596828
Title:
Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.
Authors:
Foley, Joseph W; Sidow, Arend
Abstract:
BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF's direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF's motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.
Citation:
Foley JW, Sidow A (2013) Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines. BMC Genomics 14: 720. Available: http://dx.doi.org/10.1186/1471-2164-14-720.
Publisher:
Springer Nature
Journal:
BMC Genomics
Issue Date:
20-Oct-2013
DOI:
10.1186/1471-2164-14-720
PubMed ID:
24138567
PubMed Central ID:
PMC3826616
Type:
Article
ISSN:
1471-2164
Sponsors:
We thank Cheryl Smith, Ed Grow, Noah Spies, and Erik Lehnert for critical reading of this manuscript. We are also grateful to Anshul Kundaje and Phil Lacroute for invaluable technical advice. This work was supported by the Stanford Genome Training Program (NIH/NHGRI T32 HG000044), a subcontract to ENCODE grant HG004695, and a KAUST AEA grant.
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Full metadata record

DC FieldValue Language
dc.contributor.authorFoley, Joseph Wen
dc.contributor.authorSidow, Arenden
dc.date.accessioned2016-02-21T08:51:27Zen
dc.date.available2016-02-21T08:51:27Zen
dc.date.issued2013-10-20en
dc.identifier.citationFoley JW, Sidow A (2013) Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines. BMC Genomics 14: 720. Available: http://dx.doi.org/10.1186/1471-2164-14-720.en
dc.identifier.issn1471-2164en
dc.identifier.pmid24138567en
dc.identifier.doi10.1186/1471-2164-14-720en
dc.identifier.urihttp://hdl.handle.net/10754/596828en
dc.description.abstractBACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF's direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF's motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.en
dc.description.sponsorshipWe thank Cheryl Smith, Ed Grow, Noah Spies, and Erik Lehnert for critical reading of this manuscript. We are also grateful to Anshul Kundaje and Phil Lacroute for invaluable technical advice. This work was supported by the Stanford Genome Training Program (NIH/NHGRI T32 HG000044), a subcontract to ENCODE grant HG004695, and a KAUST AEA grant.en
dc.publisherSpringer Natureen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.titleTranscription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.en
dc.typeArticleen
dc.identifier.journalBMC Genomicsen
dc.identifier.pmcidPMC3826616en
dc.contributor.institutionDepartment of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA. joseph.foley@mail.mcgill.ca.en

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