Abstract
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.
Highlights
An increasing number of studies challenged the textbook model of repressive DNA methylation that is catalysed by DNA methyltransferases (DNMTs)
DNA methyltransferase 1 (DNMT1) regulates the expression of Lhx1 noncanonically
We checked for changes in the expression levels of Lhx1 in Fluorescence-activated cell sorting (FACS)-enriched Hmx3-Cre/tdTomato/ Dnmt1 control and Hmx3-Cre/tdTomato/Dnmt1 interneurons isolated from the pre-optic area (POA) of mouse embryos at embryonic day (E) 16, at the peak of POA interneuron migration (Figure 1(a))
Summary
An increasing number of studies challenged the textbook model of repressive DNA methylation that is catalysed by DNA methyltransferases (DNMTs). DNMTs act on histone modifications by transcriptional control over genes encoding for proteins implicated in HMCs or by interacting with protein complexes independent of their DNA methylating activity [9,10,11,12]. This diversity of actions requires detailed investigations to decipher the functional implications of distinct epigenetic mechanisms in directing cell- and stage-specific differentiation and maturation programmes, and to reveal causes for dysfunctions in related diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
