GFI1 regulates hair cell differentiation by acting as an off-DNA transcriptional co-activator of ATOH1, and a DNA-binding repressor.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 05 2022
12 05 2022
Historique:
received:
19
10
2021
accepted:
03
05
2022
entrez:
13
5
2022
pubmed:
14
5
2022
medline:
18
5
2022
Statut:
epublish
Résumé
GFI1 is a zinc finger transcription factor that is necessary for the differentiation and survival of hair cells in the cochlea. Deletion of Gfi1 in mice significantly reduces the expression of hundreds of hair cell genes: this is a surprising result, as GFI1 normally acts as a transcriptional repressor by recruiting histone demethylases and methyltransferases to its targets. To understand the mechanisms by which GFI1 promotes hair cell differentiation, we used CUT&RUN to identify the direct targets of GFI1 and ATOH1 in hair cells. We found that GFI1 regulates hair cell differentiation in two distinct ways-first, GFI1 and ATOH1 can bind to the same regulatory elements in hair cell genes, but while ATOH1 directly binds its target DNA motifs in many of these regions, GFI1 does not. Instead, it appears to enhance ATOH1's transcriptional activity by acting as part of a complex in which it does not directly bind DNA. Second, GFI1 can act in its more typical role as a direct, DNA-binding transcriptional repressor in hair cells; here it represses non-hair cell genes, including many neuronal genes. Together, our results illuminate the function of GFI1 in hair cell development and hair cell reprogramming strategies.
Identifiants
pubmed: 35551236
doi: 10.1038/s41598-022-11931-0
pii: 10.1038/s41598-022-11931-0
pmc: PMC9098437
doi:
Substances chimiques
Atoh1 protein, mouse
0
Basic Helix-Loop-Helix Transcription Factors
0
DNA-Binding Proteins
0
Gfi1 protein, mouse
0
Transcription Factors
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
7793Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC014832
Pays : United States
Organisme : NIDCD NIH HHS
ID : RO1DC014832
Pays : United States
Organisme : NIDCD NIH HHS
ID : RO1 DC015829
Pays : United States
Informations de copyright
© 2022. The Author(s).
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