Molecular Cell
Volume 52, Issue 1, 10 October 2013, Pages 25-36
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Article
Distinct Properties of Cell-Type-Specific and Shared Transcription Factor Binding Sites

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Highlights

  • Two types of estrogen receptor α binding sites: shared and cell specific

  • Shared sites are encoded in the genome as high-affinity estrogen response elements

  • Cell-specific sites rely on interacting factors and depend on genomic context

  • Cell-specific binding is predicted from DNA sequence and chromatin accessibility

Summary

Most human transcription factors bind a small subset of potential genomic sites and often use different subsets in different cell types. To identify mechanisms that govern cell-type-specific transcription factor binding, we used an integrative approach to study estrogen receptor α (ER). We found that ER exhibits two distinct modes of binding. Shared sites, bound in multiple cell types, are characterized by high-affinity estrogen response elements (EREs), inaccessible chromatin, and a lack of DNA methylation, while cell-specific sites are characterized by a lack of EREs, co-occurrence with other transcription factors, and cell-type-specific chromatin accessibility and DNA methylation. These observations enabled accurate quantitative models of ER binding that suggest tethering of ER to one-third of cell-specific sites. The distinct properties of cell-specific binding were also observed with glucocorticoid receptor and for ER in primary mouse tissues, representing an elegant genomic encoding scheme for generating cell-type-specific gene regulation.

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