The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene1,2,3, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome4,5,6. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
We thank members of the Ren laboratory for comments. This work was supported by funding from American Cancer Society (R.D.H.), NIAID Intramural Research Program (V.V.L.), LICR (B.R.), NHGRI (B.R.), NCI (B.R.) and CIRM (B.R.).
Author Contributions R.D.H., N.D.H., G.C.H. and B.R. designed the experiments; R.D.H., N.D.H., L.F.H., Z.Y., L.K.L., R.K.S., C.W.C., H.L. and X.Z. conducted the ChIP-chip experiments; G.C.H. and K.A.C. analysed the ChIP-chip data; G.C.H. predicted enhancers; R.D.H. and L.K.L. conducted the reporter assays; J.E.A.-B., R.S. and J.A.T. provided human ES cells and expression data; V.V.L. provided advice and antibodies for CTCF-ChIP experiments; P.K., A.S. and M.K. analysed the transcription factor motifs; G.E.C. performed and analysed the DNaseI-chip experiments; and N.D.H., G.C.H., R.D.H. and B.R. wrote the manuscript.
This file contains Supplementary Methods, Supplementary Data, Supplementary References, Supplementary Figures S1- S14 with Legends, Supplementary Table Captions S1-S16 and Supplementary Tables S1-S16
About this article
Scientific Reports (2019)