GSE49993
Distinct properties of cell type-specific and shared transcription factor binding sites
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 a (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. Overall design: ChIP-seq of transcription factors in mouse tissues