Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex.
ACTL6A/BAF complex
epidermis
keratinocyte
lncRNA
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
04 03 2020
04 03 2020
Historique:
received:
13
07
2018
revised:
23
12
2019
accepted:
08
01
2020
pubmed:
6
2
2020
medline:
28
4
2021
entrez:
5
2
2020
Statut:
ppublish
Résumé
The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes.
Identifiants
pubmed: 32017402
doi: 10.15252/embr.201846734
pmc: PMC7054673
doi:
Substances chimiques
ACTL6A protein, human
0
Actins
0
BANF1 protein, human
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
DNA-Binding Proteins
0
RNA, Long Noncoding
0
Transcription Factors
0
Banques de données
GEO
['GSE103890']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e46734Subventions
Organisme : Fundació la Marató de TV3 (TV3 Marathon Foundation)
ID : PI043296
Pays : International
Organisme : Ministerio de Economía y Competitividad (MEC)
ID : BFU2014-55054-P
Pays : International
Organisme : Medical Research Council
ID : MC_U132670600
Pays : United Kingdom
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : 22206
Pays : International
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
ID : RIBOMYLOME_309545
Pays : International
Organisme : Medical Research Council
ID : MC_UU_00025/2
Pays : United Kingdom
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : IDI-IRCCS-RC3.2
Pays : International
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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