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Dynamic Distribution of Histone H4 Arginine 3 Methylation Marks in the Developing Murine Cortex

Chittka, A; (2010) Dynamic Distribution of Histone H4 Arginine 3 Methylation Marks in the Developing Murine Cortex. PLoS One , 5 (11) , Article e13807. 10.1371/journal.pone.0013807. Green open access

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Abstract

Background Epigenetic modifications regulate key transitions in cell fate during development of the central nervous system (CNS). During cortical development the initial population of proliferative neuroepithelial precursor cells give rise to neurons and then glia in a strict temporal order. Neurogenesis and gliogenesis are accompanied by a switch from symmetric to asymmetric divisions of the neural precursor cells generating another precursor and a differentiated progeny. To investigate whether specific post-translational histone modifications define specific stages of neural precursor differentiation during cortical development I focussed on the appearance of two different types of histone arginine methylation, the dimethyl symmetric H4R3 (H4R3me2s) and dimethyl asymmetric H4R3 (H4R3me2a) in the developing mouse cortex. Methodology/Principal Findings An immunohistochemical study of the developing cortex at different developmental stages was performed to detect the distribution of H4R3me2s and H4R3me2a modifications. I analysed the distribution of these modifications in: 1) undifferentiated neural precursors, 2) post-mitotic neurons and 3) developing oligodendrocyte precursors (OLPs) using lineage-specific and histone modification-specific antibodies to co-label the cells. I found that the proliferative neuroepithelium during the stage of mainly symmetric expansive divisions is characterised by the prevalence of H4R3me2s modification and almost no detectable H4R3me2a modification. However, at a later stage, when the cortical layers with post-mitotic neurons have begun forming, both H4R3me2a and H4R3me2s modifications are detected in the post-mitotic neurons and in the developing OLPs. Conclusions/Significance I propose that the H4R3me2s modification forms part of the “histone code” of undifferentiated neural precursors. The later appearance of the H4R3me2a modifications specifies the onset of neurogenesis and gliogenesis and the commitment of the NSCs to differentiate. Thus, the sequential appearance of the two different H4R3 methylation marks may define a particular cellular state of the NSCs during their development and differentiation demonstrating the role of histone arginine methylation in cortical development.

Type: Article
Title: Dynamic Distribution of Histone H4 Arginine 3 Methylation Marks in the Developing Murine Cortex
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0013807
Publisher version: http://dx.doi.org/10.1371/journal.pone.0013807
Language: English
Additional information: © 2010 Alexandra Chittka. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC2972221
Keywords: Animals, Arginine, Cerebral Cortex, Epithelium, Fluorescent Antibody Technique, Histones, Methylation, Mice, Neurogenesis, Neurons, Oligodendroglia, Receptor, Platelet-Derived Growth Factor alpha, Stem Cells, Time Factors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/1398279
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