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Open Access Highly Accessed Research article

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

Joseph W Foley12* and Arend Sidow13

Author Affiliations

1 Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA

2 Current address: Douglas Mental Health University Institute, McGill University, 6875 Boulevard LaSalle, Verdun, Québec H4H 1R3, Canada

3 Department of Pathology, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA

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BMC Genomics 2013, 14:720  doi:10.1186/1471-2164-14-720

Published: 20 October 2013

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.

Keywords:
Transcription factor; ChIP-seq; HOT region; Gene regulation