NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain.
Animals
Brain
/ metabolism
CREB-Binding Protein
/ genetics
Cell Differentiation
Chromatin
/ chemistry
Cytoskeletal Proteins
/ metabolism
E1A-Associated p300 Protein
/ genetics
Embryonic Stem Cells
/ metabolism
Female
Genomics
HEK293 Cells
Heterozygote
Humans
Male
Mice
Neurons
/ metabolism
Nuclear Respiratory Factor 1
/ metabolism
Protein Binding
Protein Domains
Proteomics
Transcription Factors
/ metabolism
Transcriptional Activation
AUTS2
NRF1
P300
RSTS
active transcription
brain development
ncPRC1.3
polycomb
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
18 11 2021
18 11 2021
Historique:
received:
29
03
2021
revised:
21
07
2021
accepted:
15
09
2021
pubmed:
13
10
2021
medline:
8
1
2022
entrez:
12
10
2021
Statut:
ppublish
Résumé
The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin.
Identifiants
pubmed: 34637754
pii: S1097-2765(21)00754-1
doi: 10.1016/j.molcel.2021.09.020
pmc: PMC8604784
mid: NIHMS1743382
pii:
doi:
Substances chimiques
AUTS2 protein, human
0
Auts2 protein, mouse
0
Chromatin
0
Cytoskeletal Proteins
0
NRF1 protein, human
0
Nrf1 protein, mouse
0
Nuclear Respiratory Factor 1
0
Transcription Factors
0
CREB-Binding Protein
EC 2.3.1.48
CREBBP protein, human
EC 2.3.1.48
Crebbp protein, mouse
EC 2.3.1.48
E1A-Associated p300 Protein
EC 2.3.1.48
EP300 protein, human
EC 2.3.1.48
Ep300 protein, mouse
EC 2.3.1.48
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
Pagination
4663-4676.e8Subventions
Organisme : NCI NIH HHS
ID : R01 CA199652
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024376
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS100897
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS050375
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY028102
Pays : United States
Organisme : NIAAA NIH HHS
ID : K99 AA024837
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.R. is a cofounder of Constellation and Fulcrum Pharmaceuticals.
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