Neuronal Lhx1 expression is regulated by DNMT1-dependent modulation of histone marks

Judit Symmank; Cathrin Bayer; Julia Reichard; Daniel Pensold; Geraldine Zimmer-Bensch

doi:10.1080/15592294.2020.1767372

Neuronal Lhx1 expression is regulated by DNMT1-dependent modulation of histone marks

Epigenetics. 2020 Nov;15(11):1259-1274. doi: 10.1080/15592294.2020.1767372. Epub 2020 May 22.

Authors

Judit Symmank^{1

2}, Cathrin Bayer^{1

3}, Julia Reichard^{1

3

4}, Daniel Pensold^{1

3}, Geraldine Zimmer-Bensch^{1

2

3}

Affiliations

¹ Institute for Human Genetics, Am Klinikum 1, University Hospital Jena , Jena, Germany.
² Polyclinic for Orthodontics, Leutragraben 3, University Hospital Jena , Jena, Germany.
³ Department of Functional Epigenetics in the Animal Model, Institute for Biology II, Worringerweg 3, RWTH Aachen University , Aachen, Germany.
⁴ Research Training Group 2416 MultiSenses, MultiScales, RWTH Aachen University , Aachen, Germany.

Abstract

Apart from the conventional view of repressive promoter methylation, the DNA methyltransferase 1 (DNMT1) was recently described to modulate gene expression through a variety of interactions with diverse epigenetic key players. We here investigated the DNMT1-dependent transcriptional control of the homeobox transcription factor LHX1, which we previously identified as an important regulator in cortical interneuron development. We found that LHX1 expression in embryonic interneurons originating in the embryonic pre-optic area (POA) is regulated by non-canonic DNMT1 function. Analysis of histone methylation and acetylation revealed that both epigenetic modifications seem to be implicated in the control of Lhx1 gene activity and that DNMT1 contributes to their proper establishment. This study sheds further light on the regulatory network of cortical interneuron development including the complex interplay of epigenetic mechanisms.

Keywords: DNMT1; Interneuron development; LHX1; epigenetic network; histone acetylation; histone methylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Cells, Cultured
DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
Epigenesis, Genetic
Gene Expression Regulation, Developmental
Histone Code*
Interneurons / metabolism*
LIM-Homeodomain Proteins / genetics*
LIM-Homeodomain Proteins / metabolism
Mice
Mice, Inbred C57BL
Preoptic Area / cytology
Preoptic Area / embryology
Preoptic Area / metabolism
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

LIM-Homeodomain Proteins
Lhx1 protein, mouse
Transcription Factors
DNA (Cytosine-5-)-Methyltransferase 1
Dnmt1 protein, mouse

Grants and funding

The experimental realization of this study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 368482240/GRK2416 and ZI 1224/8-1; and the IZKF (Interdisciplinary Center for Clinic and Research) Jena.