TY - JOUR
T1 - A unique bipartite Polycomb signature regulates stimulus-response transcription during development
AU - Kitazawa, Taro
AU - Machlab, Dania
AU - Joshi, Onkar
AU - Maiorano, Nicola
AU - Kohler, Hubertus
AU - Ducret, Sebastien
AU - Kessler, Sandra
AU - Gezelius, Henrik
AU - Soneson, Charlotte
AU - Papasaikas, Panagiotis
AU - López-Bendito, Guillermina
AU - Stadler, Michael B
AU - Rijli, Filippo M
PY - 2021/3
Y1 - 2021/3
N2 - Rapid cellular responses to environmental stimuli are fundamental for development and maturation. Immediate early genes can be transcriptionally induced within minutes in response to a variety of signals. How their induction levels are regulated and their untimely activation by spurious signals prevented during development is poorly understood. We found that in developing sensory neurons, before perinatal sensory-activity-dependent induction, immediate early genes are embedded into a unique bipartite Polycomb chromatin signature, carrying active H3K27ac on promoters but repressive Ezh2-dependent H3K27me3 on gene bodies. This bipartite signature is widely present in developing cell types, including embryonic stem cells. Polycomb marking of gene bodies inhibits mRNA elongation, dampening productive transcription, while still allowing for fast stimulus-dependent mark removal and bipartite gene induction. We reveal a developmental epigenetic mechanism regulating the rapidity and amplitude of the transcriptional response to relevant stimuli, while preventing inappropriate activation of stimulus-response genes.
AB - Rapid cellular responses to environmental stimuli are fundamental for development and maturation. Immediate early genes can be transcriptionally induced within minutes in response to a variety of signals. How their induction levels are regulated and their untimely activation by spurious signals prevented during development is poorly understood. We found that in developing sensory neurons, before perinatal sensory-activity-dependent induction, immediate early genes are embedded into a unique bipartite Polycomb chromatin signature, carrying active H3K27ac on promoters but repressive Ezh2-dependent H3K27me3 on gene bodies. This bipartite signature is widely present in developing cell types, including embryonic stem cells. Polycomb marking of gene bodies inhibits mRNA elongation, dampening productive transcription, while still allowing for fast stimulus-dependent mark removal and bipartite gene induction. We reveal a developmental epigenetic mechanism regulating the rapidity and amplitude of the transcriptional response to relevant stimuli, while preventing inappropriate activation of stimulus-response genes.
KW - Animals
KW - Chromatin/genetics
KW - Embryonic Stem Cells/physiology
KW - Enhancer of Zeste Homolog 2 Protein/genetics
KW - Epigenesis, Genetic
KW - Gene Expression Regulation, Developmental
KW - Genes, Immediate-Early
KW - Histones/metabolism
KW - Mice, Transgenic
KW - Mutation
KW - Polycomb-Group Proteins/genetics
KW - Promoter Regions, Genetic
KW - RNA Polymerase II/genetics
KW - RNA, Messenger/genetics
KW - Rhombencephalon/drug effects
KW - Sensory Receptor Cells/physiology
UR - http://www.scopus.com/inward/record.url?scp=85101206850&partnerID=8YFLogxK
U2 - 10.1038/s41588-021-00789-z
DO - 10.1038/s41588-021-00789-z
M3 - Journal article
C2 - 33603234
SN - 1061-4036
VL - 53
SP - 379
EP - 391
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -