The transcription factor GLI1 cooperates with the chromatin remodeler SMARCA2 to regulate chromatin accessibility at distal DNA regulatory elements.
Cell Line, Tumor
Chromatin
/ genetics
Chromatin Assembly and Disassembly
DNA
/ genetics
HEK293 Cells
Humans
Protein Domains
Protein Interaction Maps
Regulatory Elements, Transcriptional
Transcription Factors
/ chemistry
Transcription Initiation Site
Transcriptional Activation
Zinc Finger Protein GLI1
/ chemistry
ATAC-seq
GLI family zinc finger 1 (GLI1)
SWI/SNF related
actin dependent regulator of chromatin
cancer
cancer cells
chromatin
chromatin remodeling
enhancer
epigenetic regulation
gene transcription
matrix associated
member 2 (SMARCA2)
subfamily A
transcription enhancer
transcriptomics
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
26 06 2020
26 06 2020
Historique:
received:
01
03
2020
revised:
04
05
2020
pubmed:
8
5
2020
medline:
14
1
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
The transcription factor GLI1 (GLI family zinc finger 1) plays a key role in the development and progression of multiple malignancies. To date, regulation of transcriptional activity at target gene promoters is the only molecular event known to underlie the oncogenic function of GLI1. Here, we provide evidence that GLI1 controls chromatin accessibility at distal regulatory regions by modulating the recruitment of SMARCA2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2) to these elements. We demonstrate that SMARCA2 endogenously interacts with GLI1 and enhances its transcriptional activity. Mapping experiments indicated that the C-terminal transcriptional activation domain of GLI1 and SMARCA2's central domains, including its ATPase motif, are required for this interaction. Interestingly, similar to SMARCA2, GLI1 overexpression increased chromatin accessibility, as indicated by results of the micrococcal nuclease assay. Further, results of assays for transposase-accessible chromatin with sequencing (ATAC-seq) after GLI1 knockdown supported these findings, revealing that GLI1 regulates chromatin accessibility at several regions distal to gene promoters. Integrated RNA-seq and ATAC-seq data analyses identified a subset of differentially expressed genes located in
Identifiants
pubmed: 32376693
pii: S0021-9258(17)49368-9
doi: 10.1074/jbc.RA120.013268
pmc: PMC7324497
pii:
doi:
Substances chimiques
Chromatin
0
GLI1 protein, human
0
SMARCA2 protein, human
0
Transcription Factors
0
Zinc Finger Protein GLI1
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
8725-8735Subventions
Organisme : NCI NIH HHS
ID : R01 CA136526
Pays : United States
Informations de copyright
© 2020 Safgren et al.
Déclaration de conflit d'intérêts
Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article.
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