Interplay between H1 and HMGN epigenetically regulates OLIG1&2 expression and oligodendrocyte differentiation
| Autor: | Tao Deng, Shaofei Zhang, Valerie Gailus-Durner, Helmut Fuchs, Lore Becker, Martin Hrabé de Angelis, Wolfgang Wurst, Yuri V. Postnikov, Ildiko Racz, Lillian Garrett, Michael Bustin, Sabine M. Hölter |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male genetics [HMGN2 Protein] metabolism [Histones] Oligodendrocyte Transcription Factor 2 HMGN Proteins Epigenesis Genetic Histones Mice 0302 clinical medicine metabolism [Embryonic Stem Cells] Basic Helix-Loop-Helix Transcription Factors genetics [Nerve Tissue Proteins] Mice Knockout genetics [Cell Differentiation] Chromatin binding metabolism [Enhancer of Zeste Homolog 2 Protein] Cell Differentiation Chromatin Cell biology Oligodendroglia Ezh2 protein mouse physiology [HMGN Proteins] Histone methyltransferase ddc:540 Female genetics [HMGN1 Protein] HMGN2 Protein genetics [Basic Helix-Loop-Helix Transcription Factors] Nerve Tissue Proteins Biology Cell Line OLIG2 03 medical and health sciences Genetics Animals Enhancer of Zeste Homolog 2 Protein cytology [Oligodendroglia] Olig2 protein mouse Embryonic Stem Cells physiology [HMGN2 Protein] metabolism [Nerve Tissue Proteins] Gene regulation Chromatin and Epigenetics Oligodendrocyte differentiation HMGN Olig1 protein mouse metabolism [Basic Helix-Loop-Helix Transcription Factors] 030104 developmental biology physiology [HMGN1 Protein] 030217 neurology & neurosurgery HMGN1 Protein |
| Zdroj: | Nucleic acids symposium series 45(6), 3031-3045 (2016). doi:10.1093/nar/gkw1222 Nucleic Acids Research Nucleic Acids Res. 45, 3031-3045 (2017) ResearcherID |
| DOI: | 10.1093/nar/gkw1222 |
| Popis: | An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination. Loss of HMGNs increases the chromatin binding of histone H1, thereby recruiting the histone methyltransferase EZH2 and elevating H3K27me3 levels, thus conferring a repressive epigenetic signature at Olig1&2 sites. Embryonic stem cells lacking HMGNs show reduced ability to differentiate towards the oligodendrocyte lineage, and mice lacking HMGNs show reduced oligodendrocyte count and decreased spinal cord myelination, and display related neurological phenotypes. Thus, the presence of HMGN proteins is required for proper expression of neural differentiation genes during embryonic stem cell differentiation. Specifically, we demonstrate that the dynamic interplay between HMGNs and H1 in chromatin epigenetically regulates the expression of OLIG1&2, thereby affecting oligodendrocyte development and myelination, and mouse behavior. |
| Databáze: | OpenAIRE |
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