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

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:

• Interneuron development
• LHX1
• DNMT1
• histone methylation
• histone acetylation
• epigenetic network

Disclosure statement

The authors declare that they have no competing interest.

Authors´ contribution

JS: designed and performed experiments, data analysis, figure illustration, conceptual design of the study, wrote the manuscript; CB: performed experiments, data analysis, figure illustration, corrected the manuscript; JR: performed experiments, data analysis, figure illustration, corrected the manuscript; DP: performed experiments and data analysis; corrected the manuscript; GZ, conceptual design of the study results, discussion, wrote the manuscript. All authors read and approved the manuscript.

Availability of data and materials

The reanalyzed RNA sequencing and MeDIP data sets comparing Hmx3-Cre/tdTomato/Dnmt1 wild-type as well as Hmx3-Cre/tdTomato/Dnmt1 loxP² mice that are used in this study are published by Pensold et al. (27) and uploaded at GEO with the series number GSE146968.

Additional information

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.