Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Abstract

Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.

JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states

“…We clustered TSS separated by less that 500 nt and selected the center and strand of strongest TSS/DPI as a representative for a given group of TSS cluster, which led to the selection of 21,251 centers with strand information (representing 14,685 out of 24,045 merged acetylation peaks). Second, we overlapped the remaining 9,360 acetyl peaks with bidirectionally transcribed enhancer annotated from FANTOM5 [71,72] and found 3,161 enhancer-overlapping 2,448 acetyl sites. We clustered enhancer separated by less that 500 nt and selected the strongest enhancer within each group, 2,815 in total.…”

Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain

“…PC inhibition of CBP at enhancers of PC-regulated genes may also regulate the onset of enhancer transcription, which has been reported to be impaired by p300 knockdown (59). Recent genomewide temporal profiling of enhancer transcription revealed that a rapid burst of it, accompanied by enrichment of the H3K27ac mark on enhancers, occurs just before transcription from the promoters of their associated genes and is the most common initial transcription event genome-wide (60).…”

Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia

“…Enhancers represent key control switches that regulate initiation of transcription at nearby gene loci by integrating signals from multiple TFs (Arner et al 2015). Transcription of eRNA is considered the most precise mark of functional looping between an activated enhancer and its regulated gene promoter, and the dynamic changes observed in eRNA levels allow elucidation of key TFs upon cell differentiation and environmental stimuli (Wang et al 2011;Kaikkonen et al 2013).…”