Temporal expression of MOF acetyltransferase primes transcription factor networks for erythroid fate.

Science Advances
Cecilia Pessoa RodriguesA Akhtar

Abstract

Self-renewal and differentiation of hematopoietic stem cells (HSCs) are orchestrated by the combinatorial action of transcription factors and epigenetic regulators. Here, we have explored the mechanism by which histone H4 lysine 16 acetyltransferase MOF regulates erythropoiesis. Single-cell RNA sequencing and chromatin immunoprecipitation sequencing uncovered that MOF influences erythroid trajectory by dynamic recruitment to chromatin and its haploinsufficiency causes accumulation of a transient HSC population. A regulatory network consisting of MOF, RUNX1, and GFI1B is critical for erythroid fate commitment. GFI1B acts as a Mof activator which is necessary and sufficient for cell type-specific induction of Mof expression. Plasticity of Mof-depleted HSCs can be rescued by expression of a downstream effector, Gata1, or by rebalancing acetylation via a histone deacetylase inhibitor. Accurate timing and dosage of Mof expression act as a rheostat for the feedforward transcription factor network that safeguards progression along the erythroid fate.

References

Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y FujiwaraS H Orkin
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shin-Ichi Tsukumo, Koji Yasutomo
Feb 14, 2006·Science·Michael Shogren-KnaakCraig L Peterson
Mar 24, 2007·Nature Reviews. Molecular Cell Biology·Kenneth K Lee, Jerry L Workman
Oct 31, 2007·Briefings in Functional Genomics & Proteomics·Roland H FriedelWolfgang Wurst
Jan 22, 2008·Nature Immunology·Elaine Dzierzak, Nancy A Speck
Mar 29, 2008·Cell Stem Cell·Stuart M ChambersMargaret A Goodell
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
May 9, 2012·Cell Stem Cell·Maria Carolina FlorianHartmut Geiger
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Apr 3, 2013·Cold Spring Harbor Perspectives in Medicine·Elaine Dzierzak, Sjaak Philipsen
Oct 22, 2013·Nature·Maria Carolina FlorianHartmut Geiger
Jan 31, 2014·Frontiers in Physiology·James Palis
Mar 29, 2014·Frontiers in Immunology·Michelle L RatliffCarol F Webb
Apr 3, 2014·Cold Spring Harbor Perspectives in Biology·Edward Seto, Minoru Yoshida
May 21, 2014·ELife·Tomasz ChelmickiAsifa Akhtar
Aug 12, 2014·Science·David Lara-AstiasoIdo Amit
Dec 4, 2014·Therapeutic Advances in Hematology·Claudia V Andreu-Vieyra, James R Berenson
Feb 19, 2016·Genome Biology·Tomislav IlicicSarah A Teichmann
Mar 24, 2016·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Kristy WahaibPatrick D Ford
Apr 16, 2016·Nucleic Acids Research·Fidel RamírezThomas Manke
Apr 29, 2016·Genome Biology·Tamar HashimshonyItai Yanai
Jun 30, 2016·Scientific Reports·Hui ShiFeng-Chun Yang
Feb 10, 2017·Blood·Raman SoodPaul Liu

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Citations

Jan 30, 2021·Seminars in Hematology·Sriram SundaravelAmittha Wickrema

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Datasets Mentioned

BETA
GSE74912

Methods Mentioned

BETA
immunoprecipitation
scRNA-seq
acetylation
Histone acetylation
enzyme-linked immunosorbent assay
fluorescence-activated cell sorting
flow cytometry
ChIP-seq
ChIP
transfection

Software Mentioned

FlowJo
Galaxy
deepTools2
Prism
BEDtools sort
Bioconductor
ImageJ
Jupyter
comptsne
clustdiffgenes

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