Master lineage transcription factors anchor trans mega transcriptional complexes at highly accessible enhancer sites to promote long-range chromatin clustering and transcription of distal target genes

Autor: Michael Snyder, Shannon M White, Chunling Yi
Rok vydání: 2021
Předmět:
Zdroj: Nucleic Acids Research
ISSN: 1362-4962
0305-1048
DOI: 10.1093/nar/gkab1105
Popis: The term ‘super enhancers’ (SE) has been widely used to describe stretches of closely localized enhancers that are occupied collectively by large numbers of transcription factors (TFs) and co-factors, and control the transcription of highly-expressed genes. Through integrated analysis of >600 DNase-seq, ChIP-seq, GRO-seq, STARR-seq, RNA-seq, Hi-C and ChIA-PET data in five human cancer cell lines, we identified a new class of autonomous SEs (aSEs) that are excluded from classic SE calls by the widely used Rank Ordering of Super-Enhancers (ROSE) method. TF footprint analysis revealed that compared to classic SEs and regular enhancers, aSEs are tightly bound by a dense array of master lineage TFs, which serve as anchors to recruit additional TFs and co-factors in trans. In addition, aSEs are preferentially enriched for Cohesins, which likely involve in stabilizing long-distance interactions between aSEs and their distal target genes. Finally, we showed that aSEs can be reliably predicted using a single DNase-seq data or combined with Mediator and/or P300 ChIP-seq. Overall, our study demonstrates that aSEs represent a unique class of functionally important enhancer elements that distally regulate the transcription of highly expressed genes.
Databáze: OpenAIRE