Interplay between H1 and HMGN epigenetically regulates OLIG1&2 expression and oligodendrocyte differentiation

被引：33

作者：

Deng, Tao ^{[1
]}

Postnikov, Yuri ^{[1
]}

Zhang, Shaofei ^{[1
]}

Garrett, Lillian ^{[2
,3
,4
]}

Becker, Lore ^{[2
,3
]}

Racz, Ildiko ^{[2
,3
,5
]}

Hoelter, Sabine M. ^{[2
,3
,4
]}

Wurst, Wolfgang ^{[4
,6
,7
,8
]}

Fuchs, Helmut ^{[2
,3
]}

Gailus-Durner, Valerie ^{[2
,3
]}

de Angelis, Martin Hrabe ^{[2
,3
,9
,10
]}

Bustin, Michael ^{[1
]}

机构：

[1] NIH, Prot Sect, Lab Metab, Ctr Canc Res,NCI, Bethesda, MD 20892 USA

[2] Helmholtz Zentrum, German Mouse Clin, Inst Expt Genet, Munich, Germany

[3] German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

[4] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Dev Genet, D-85764 Neuherberg, Germany

[5] Univ Bonn, Inst Mol Psychiat, D-53125 Bonn, Germany

[6] Tech Univ Munchen Weihenstephan, Helmholtz Zentrum Munchen, Chair Dev Genet, D-85764 Neuherberg, Germany

[7] German Ctr Neurodegenerat Dis DZNE Site Munich, Munich, Germany

[8] Ludwig Maximilians Univ Munchen, Adolf Butenandt Inst, Munich Cluster Syst Neurol SyNergy, D-80336 Munich, Germany

[9] Tech Univ Munich, Sch Life Sci Weihenstephan, Chair Expt Genet, D-85354 Freising Weihenstephan, Germany

[10] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany

来源：

NUCLEIC ACIDS RESEARCH | 2017年 / 45卷 / 06期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; HISTONE H1; CHROMATIN-BINDING; CHROMOSOMAL-PROTEINS; NERVOUS-SYSTEM; LINKER HISTONE; OPEN-FIELD; MOBILITY; MYELINATION; DYNAMICS;

D O I：

10.1093/nar/gkw1222

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 dif-ferentiation. 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.

引用

页码：3031 / 3045

页数：15

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