Show simple item record

dc.contributor.authorFoley, Joseph W
dc.contributor.authorSidow, Arend
dc.date.accessioned2016-02-21T08:51:27Z
dc.date.available2016-02-21T08:51:27Z
dc.date.issued2013-10-20
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.
dc.identifier.issn1471-2164
dc.identifier.pmid24138567
dc.identifier.doi10.1186/1471-2164-14-720
dc.identifier.urihttp://hdl.handle.net/10754/596828
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.
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.
dc.publisherSpringer Nature
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.
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleTranscription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.
dc.typeArticle
dc.identifier.journalBMC Genomics
dc.identifier.pmcidPMC3826616
dc.contributor.institutionDepartment of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA. joseph.foley@mail.mcgill.ca.
refterms.dateFOA2018-06-13T14:09:42Z


Files in this item

Thumbnail
Name:
PMC3826616.pdf
Size:
3.246Mb
Format:
PDF
Description:
Main article

This item appears in the following Collection(s)

Show simple item record

This 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.
Except where otherwise noted, this item's license is described as This 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.