The histone demethylase Kdm3a is essential to progression through differentiation.

Nucleic Acids Research
Marielle HerzogFrançois Fuks

Abstract

Histone demethylation has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity by still poorly understood mechanisms. Here, we examined the role of histone demethylase Kdm3a during cell differentiation, showing that Kdm3a is essential for differentiation into parietal endoderm-like (PE) cells in the F9 mouse embryonal carcinoma model. We identified a number of target genes regulated by Kdm3a during endoderm differentiation; among the most dysregulated were the three developmental master regulators Dab2, Pdlim4 and FoxQ1. We show that dysregulation of the expression of these genes correlates with Kdm3a H3K9me2 demethylase activity. We further demonstrate that either Dab2 depletion or Kdm3a depletion prevents F9 cells from fully differentiating into PE cells, but that ectopic expression of Dab2 cannot compensate for Kdm3a knockdown; Dab2 is thus necessary, but insufficient on its own, to promote complete terminal differentiation. We conclude that Kdm3a plays a crucial role in progression through PE differentiation by regulating expression of a set of endoderm differentiation master genes. The emergence of Kdm3a as a key modulator of cell fate decision s...Continue Reading

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Citations

Feb 21, 2014·Molecular Biology of the Cell·Ioannis KasioulisPatricia L Yeyati
Apr 3, 2015·Epigenomics·Rebecca L HancockAkane Kawamura
Dec 19, 2015·Stem Cells International·Fizzah Aziz Choudry, Mattia Frontini
Jan 15, 2013·Biochemical and Biophysical Research Communications·Kumi MorikawaYasuaki Shirayoshi
Sep 28, 2014·Experimental Cell Research·Isabel Beerman, Derrick J Rossi
Apr 30, 2017·Experimental & Molecular Medicine·Hongjie ShenFei Lan
Nov 20, 2017·Tissue Engineering and Regenerative Medicine·Ji Eun Lim, Youngsook Son
Feb 9, 2021·Biochimica Et Biophysica Acta. General Subjects·Lei WangMichael J Soares
Aug 6, 2021·Journal of Cellular and Molecular Medicine·Qian XuLili Lu
Sep 14, 2021·Biology of Reproduction·Jocelyn M CuthbertAbby D Benninghoff

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Datasets Mentioned

BETA
GSE33841

Methods Mentioned

BETA
acetylation
PCR
Assay
ChIP
reverse-transcription PCR
transfection

Software Mentioned

gplots
limma
beadarray
R

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