Transcriptional response to stress is pre-wired by promoter and enhancer architecture

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Vihervaara A, Mahat DB, Guertin MJ, Chu TY, Danko CG, Lis JT, Sistonen L
Publiceringsår: 2017
Tidskrift: Nature Communications
Tidskriftsakronym: NAT COMMUN
Volym: 8
Antal sidor: 16
ISSN: 2041-1723
eISSN: 2041-1723


Programs of gene expression are executed by a battery of transcription factors that coordinate divergent transcription from a pair of tightly linked core initiation regions of promoters and enhancers. Here, to investigate how divergent transcription is reprogrammed upon stress, we measured nascent RNA synthesis at nucleotide-resolution, and profiled histone H4 acetylation in human cells. Our results globally show that the release of promoter-proximal paused RNA polymerase into elongation functions as a critical switch at which a gene's response to stress is determined. Highly transcribed and highly inducible genes display strong transcriptional directionality and selective assembly of general transcription factors on the core sense promoter. Heat-induced transcription at enhancers, instead, correlates with prior binding of cell-type, sequence-specific transcription factors. Activated Heat Shock Factor 1 (HSF1) binds to transcription-primed promoters and enhancers, and CTCF-occupied, non-transcribed chromatin. These results reveal chromatin architectural features that orient transcription at divergent regulatory elements and prime transcriptional responses genome-wide.

Senast uppdaterad 2019-23-09 vid 02:36