Histone H3.3 phosphorylation amplifies stimulation-induced transcription.

Nature
Anja ArmacheSteven Z Josefowicz

Abstract

Complex organisms can rapidly induce select genes in response to diverse environmental cues. This regulation occurs in the context of large genomes condensed by histone proteins into chromatin. The sensing of pathogens by macrophages engages conserved signalling pathways and transcription factors to coordinate the induction of inflammatory genes1-3. Enriched integration of histone H3.3, the ancestral histone H3 variant, is a general feature of dynamically regulated chromatin and transcription4-7. However, how chromatin is regulated at induced genes, and what features of H3.3 might enable rapid and high-level transcription, are unknown. The amino terminus of H3.3 contains a unique serine residue (Ser31) that is absent in 'canonical' H3.1 and H3.2. Here we show that this residue, H3.3S31, is phosphorylated (H3.3S31ph) in a stimulation-dependent manner along rapidly induced genes in mouse macrophages. This selective mark of stimulation-responsive genes directly engages the histone methyltransferase SETD2, a component of the active transcription machinery, and 'ejects' the elongation corepressor ZMYND118,9. We propose that features of H3.3 at stimulation-induced genes, including H3.3S31ph, provide preferential access to the transcr...Continue Reading

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Citations

Aug 31, 2020·Signal Transduction and Targeted Therapy·Hong Wen, Xiaobing Shi
Oct 8, 2020·Epigenetics & Chromatin·Saikat Bhattacharya, Jerry L Workman
Oct 15, 2020·Open Biology·Amanuel Tafessu, Laura A Banaszynski
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Nov 21, 2020·Cells·Imtiaz Nisar LoneHani Alotaibi
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Mar 2, 2021·Immunological Reviews·Alexia Martínez de Paz, Steven Zvi Josefowicz
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Apr 4, 2021·Cells·Susanne BacherM Lienhard Schmitz
Apr 17, 2021·Molecular Cell·Markus Nevil, Robert J Duronio
May 8, 2021·Frontiers in Cell and Developmental Biology·Reuben FranklinSihem Cheloufi
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Mar 31, 2021·Annual Review of Genomics and Human Genetics·Paul B Talbert, Steven Henikoff
Sep 12, 2020·Cancer Cell·Richard E PhillipsC David Allis

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Methods Mentioned

BETA
RNA-seq
ChIP
immunoprecipitation
isothermal titration calorimetry
PCR
fluorescence imaging
transfection
FACS
flow cytometry
size-exclusion chromatography

Software Mentioned

plot
COOT
bigWig
Trim Galore
ngs
R
IGV
HKL2000
clusterProfiler
enrichGO

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