The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression program to control neurite outgrowth
- St Jude Children's Research Hospital, United States
- Washington University in St Louis, United States
Abstract
The mitotic deacetylase complex (MiDAC) is a recently identified histone deacetylase (HDAC) complex. While other HDAC complexes have been implicated in neurogenesis, the physiological role of MiDAC remains unknown. Here, we show that MiDAC constitutes an important regulator of neural differentiation. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC upregulates gene expression of pro-neural genes such as those encoding the secreted ligands SLIT3 and NETRIN1 (NTN1) by a mechanism suggestive of H4K20ac removal on promoters and enhancers. Conversely, MiDAC inhibits gene expression by reducing H3K27ac on promoter-proximal and -distal elements of negative regulators of neurogenesis. Furthermore, loss of MiDAC results in neurite outgrowth defects that can be rescued by supplementation with SLIT3 and/or NTN1. These findings indicate a crucial role for MiDAC in regulating the ligands of the SLIT3 and NTN1 signaling axes to ensure the proper integrity of neurite development.
Data availability
RNA-sequencing and ChIP-sequencing data have been deposited in GEO under the accession code GSE131062. All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Shondra M Pruett-Miller
Funding
National Cancer Institute
- Hans-Martin Herz
American Lebanese Syrian Associated Charities
- Hans-Martin Herz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jessica K Tyler, Weill Cornell Medicine, United States
Version history
- Received: April 7, 2020
- Accepted: April 7, 2020
- Accepted Manuscript published: April 16, 2020 (version 1)
- Version of Record published: April 30, 2020 (version 2)
- Version of Record updated: May 26, 2020 (version 3)
Copyright
© 2020, Mondal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression program to control neurite outgrowth
eLife 9:e57519.
https://doi.org/10.7554/eLife.57519
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