TY - JOUR
T1 - Transcriptional response to stress is pre-wired by promoter and enhancer architecture
AU - Vihervaara, Anniina
AU - Mahat, Dig Bijay
AU - Guertin, Michael J
AU - Chu, Tinyi
AU - Danko, Charles G
AU - Lis, John T
AU - Sistonen, Lea
PY - 2017/8/15
Y1 - 2017/8/15
N2 - 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.Heat Shock Factor 1 (HSF1) is a regulator of stress-induced transcription. Here, the authors investigate changes to transcription and chromatin organization upon stress and find that activated HSF1 binds to transcription-primed promoters and enhancers, and to CTCF occupied, untranscribed chromatin.
AB - 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.Heat Shock Factor 1 (HSF1) is a regulator of stress-induced transcription. Here, the authors investigate changes to transcription and chromatin organization upon stress and find that activated HSF1 binds to transcription-primed promoters and enhancers, and to CTCF occupied, untranscribed chromatin.
KW - Acetylation
KW - Cell Line
KW - Enhancer Elements, Genetic
KW - Gene Expression Regulation
KW - Heat-Shock Proteins/genetics
KW - Heat-Shock Response
KW - Humans
KW - Promoter Regions, Genetic
KW - Stress, Physiological
KW - Transcription Factors/genetics
KW - Transcription, Genetic
U2 - 10.1038/s41467-017-00151-0
DO - 10.1038/s41467-017-00151-0
M3 - Article
C2 - 28811569
SN - 2041-1723
VL - 8
SP - 255
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -