TY - JOUR
T1 - An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output during C. elegans Development
AU - Stec, Natalia
AU - Doerfel, Katja
AU - Hills-Muckey, Kelly
AU - Ettorre, Victoria M.
AU - Ercan, Sevinc
AU - Keil, Wolfgang
AU - Hammell, Christopher M.
N1 - Funding Information:
C. elegans strains were maintained on standard media at 20°C and fed E. coli OP50. 72 A list of strains used in this study is provided in the Key Resources Table . Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). blmp-1(tm548) was obtained from Shohei Mitani the National BioResource Project (NBRP) at the Tokyo Women’s Medical University.
Funding Information:
We thank A. Zinovyeva, V. Ambros, L.M. Kutscher, and members of the Hammell laboratory for critical review of this manuscript. We received C. elegans strains and recombinant DNAs from S. Gasser, O. Hobert, and L. Cochella. The ATIP/Avenir Young Investigator program of the CNRS supported W.K. W.K. initiated and performed part of this work while being a postdoctoral fellow in the laboratories of Shai Shaham and Eric D. Siggia at Rockefeller University, supported by NIH grant R35NS105094 to Shai Shaham, NSF grant PHY 1502151 to Eric D. Siggia, and a postdoctoral fellowship ( LT000250/2013-C ) from the Human Frontier Science Program (HFSP) to W.K. Cold Spring Harbor Laboratory , the Rita Allen Foundation , and NIH NIGMS R01GM117406 supported C.M.H.
Funding Information:
We thank A. Zinovyeva, V. Ambros, L.M. Kutscher, and members of the Hammell laboratory for critical review of this manuscript. We received C. elegans strains and recombinant DNAs from S. Gasser, O. Hobert, and L. Cochella. The ATIP/Avenir Young Investigator program of the CNRS supported W.K. W.K. initiated and performed part of this work while being a postdoctoral fellow in the laboratories of Shai Shaham and Eric D. Siggia at Rockefeller University, supported by NIH grant R35NS105094 to Shai Shaham, NSF grant PHY 1502151 to Eric D. Siggia, and a postdoctoral fellowship (LT000250/2013-C) from the Human Frontier Science Program (HFSP) to W.K. Cold Spring Harbor Laboratory, the Rita Allen Foundation, and NIH NIGMS R01GM117406 supported C.M.H. N.S. W.K. and C.M.H. designed, performed, and analyzed most experiments and wrote the manuscript. ChIP-seq experiments were performed by V.M.E. and S.E. C.M.H. and K.H.-M. analyzed sequencing data. Gel shift experiments were carried out by K.D. Reporter construction and gene expression analysis were carried out by C.M.H. N.S. and K.D. Microfluidics experiments were carried out by W.K. Starvation experiments and LacO/LacI experiments were carried out by N.S. and C.M.H. The authors declare no competing interests.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/2/22
Y1 - 2021/2/22
N2 - Although precise tuning of gene expression levels is critical for most developmental pathways, the mechanisms by which the transcriptional output of dosage-sensitive molecules is established or modulated by the environment remain poorly understood. Here, we provide a mechanistic framework for how the conserved transcription factor BLMP-1/Blimp1 operates as a pioneer factor to decompact chromatin near its target loci during embryogenesis (hours prior to major transcriptional activation) and, by doing so, regulates both the duration and amplitude of subsequent target gene transcription during post-embryonic development. This priming mechanism is genetically separable from the mechanisms that establish the timing of transcriptional induction and functions to canalize aspects of cell-fate specification, animal size regulation, and molting. A key feature of the BLMP-1-dependent transcriptional priming mechanism is that chromatin decompaction is initially established during embryogenesis and maintained throughout larval development by nutrient sensing. This anticipatory mechanism integrates transcriptional output with environmental conditions and is essential for resuming normal temporal patterning after animals exit nutrient-mediated developmental arrests.
AB - Although precise tuning of gene expression levels is critical for most developmental pathways, the mechanisms by which the transcriptional output of dosage-sensitive molecules is established or modulated by the environment remain poorly understood. Here, we provide a mechanistic framework for how the conserved transcription factor BLMP-1/Blimp1 operates as a pioneer factor to decompact chromatin near its target loci during embryogenesis (hours prior to major transcriptional activation) and, by doing so, regulates both the duration and amplitude of subsequent target gene transcription during post-embryonic development. This priming mechanism is genetically separable from the mechanisms that establish the timing of transcriptional induction and functions to canalize aspects of cell-fate specification, animal size regulation, and molting. A key feature of the BLMP-1-dependent transcriptional priming mechanism is that chromatin decompaction is initially established during embryogenesis and maintained throughout larval development by nutrient sensing. This anticipatory mechanism integrates transcriptional output with environmental conditions and is essential for resuming normal temporal patterning after animals exit nutrient-mediated developmental arrests.
KW - oscillatory transcription
KW - pioneer transcription factor
KW - temporal patterning
KW - transcriptional activation
KW - Chromatin
KW - Animals
KW - Caenorhabditis elegans/genetics
KW - Transcription Factors/metabolism
KW - Gene Expression Regulation, Developmental
KW - Epigenesis, Genetic
KW - Nutrients
KW - Caenorhabditis elegans Proteins/genetics
UR - http://www.scopus.com/inward/record.url?scp=85099237073&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099237073&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2020.11.060
DO - 10.1016/j.cub.2020.11.060
M3 - Article
C2 - 33357451
AN - SCOPUS:85099237073
SN - 0960-9822
VL - 31
SP - 809-826.e6
JO - Current Biology
JF - Current Biology
IS - 4
ER -