Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization

Abstract

Recent epigenomic studies have predicted thousands of potential enhancers in the human genome. However, there has not been systematic characterization of target promoters for these potential enhancers. Using H3K4me2 as a mark for active enhancers, we identified genome-wide EP interactions in human CD4 + T cells. Among the 6 520 longdistance chromatin interactions, we identify 2 067 enhancers that interact with 1 619 promoters and enhance their expression. These enhancers exist in accessible chromatin regions and are associated with various histone modifications and polymerase II binding. The promoters with interacting enhancers are expressed at higher levels than those without interacting enhancers, and their expression levels are positively correlated with the number of interacting enhancers. Interestingly, interacting promoters are co-expressed in a tissue-specific manner. We also find that chromosomes are organized into multiple levels of interacting domains. Our results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization. The Gene Expression Omnibus accession number for the raw and analyzed chromatin interaction data is GSE32677.

High-resolution analysis of cis -acting regulatory networks at the α-globin locus

“…The lack of such a signal in the non-erythroid tissues demonstrates that this is not a random interaction and is not due to cross-hybridization with the amplified HBA promoter. This comparison between chromatin derived from expressing and non-expressing cells shows that when both the HBM and HBA genes are active, their promoters frequently interact, which has been reported for other active promoters [26][27][28].…”

Topologically-associating domains: gene warehouses adapted to serve transcriptional regulation

“…Such spatially functional networks have indeed been observed. 27,28 The possibility to establish long-distance enhancer-promoter contacts is obviously restricted by the partitioning of chromosomes into TADs. For this reason, the above described regulatory domains (regulatory archipelagos) generally colocalize with TADs.…”

Chromatin and epigenetics in all their states: Meeting report of the first conference on Epigenetic and Chromatin Regulation of Plant Traits - January 14 – 15, 2016 - Strasbourg, France

“…Through this approach, they found that enhancer transcription is preceding gene promoter transcription, challenging the previous idea that enhancers and promoters were co-expressed. 45 Therefore, upon cell differentiation, enhancers were transcribed first, followed by genes coding for TFs, and finally by genes coding for proteins other than TFs. All together, these findings bring a global view of the complex and dynamic transcriptional changes occurring during cell differentiation in mammals.…”