The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors

PLoS Genetics
Linya YouXiang-Jiao Yang

Abstract

Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regu...Continue Reading

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Citations

Oct 27, 2015·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Nuno R ZilhãoDorret I Boomsma
Sep 24, 2015·Future Medicinal Chemistry·Peter J Brown, Susanne Müller
Aug 9, 2016·The Journal of Clinical Investigation·Linya YouXiang-Jiao Yang
Feb 6, 2017·Genomics, Proteomics & Bioinformatics·Alicia Tapias, Zhao-Qi Wang
Apr 7, 2019·Cellular and Molecular Life Sciences : CMLS·Lin LiXiang-Jiao Yang
Dec 4, 2019·The Journal of Clinical Investigation·Lin LiXiang-Jiao Yang
Mar 17, 2015·The Journal of Biological Chemistry·Linya YouXiang-Jiao Yang
Nov 13, 2019·Structure·Brianna J KleinTatiana G Kutateladze
Mar 2, 2021·Frontiers in Pediatrics·Junxian FuGuanglu Yang
Mar 5, 2021·Reviews in the Neurosciences·Harish IyerArvind Kumar
Jun 3, 2021·Cancers·Ruicen HeKarl Riabowol

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Methods Mentioned

BETA
acetylation
PCR
histone acetylation
genotyping
affinity-purification

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