The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression program to control neurite outgrowth.
DNTTIP1
ELMSAN1/MIDEAS
H3K27 acetylation
H4K20 acetylation
HDAC1
SLIT and NETRIN signaling pathways
chromosomes
gene expression
mitotic deacetylase complex MiDAC
mouse
neurite ourgrowth
neuroscience
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
16 04 2020
16 04 2020
Historique:
received:
07
04
2020
accepted:
07
04
2020
pubmed:
17
4
2020
medline:
1
4
2021
entrez:
17
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32297854
doi: 10.7554/eLife.57519
pii: 57519
pmc: PMC7192582
doi:
pii:
Substances chimiques
Membrane Proteins
0
Slit3 protein, mouse
0
Netrin-1
158651-98-0
Histone Deacetylases
EC 3.5.1.98
Banques de données
GEO
['GSE131062', 'GSE55437']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R00 CA181506
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA023944
Pays : United States
Informations de copyright
© 2020, Mondal et al.
Déclaration de conflit d'intérêts
BM, HJ, SK, YS, TM, MS, GP, CL, YF, SP, HH No competing interests declared
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