Conserved Gsx2/Ind homeodomain monomer versus homodimer DNA binding defines regulatory outcomes in flies and mice.
CUT&RUN
Gsx2
Ind
lateral ganglionic eminence (LGE)
transcriptional activation versus repression
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
received:
28
07
2020
accepted:
19
11
2020
pubmed:
19
12
2020
medline:
5
8
2021
entrez:
18
12
2020
Statut:
ppublish
Résumé
How homeodomain proteins gain sufficient specificity to control different cell fates has been a long-standing problem in developmental biology. The conserved Gsx homeodomain proteins regulate specific aspects of neural development in animals from flies to mammals, and yet they belong to a large transcription factor family that bind nearly identical DNA sequences in vitro. Here, we show that the mouse and fly Gsx factors unexpectedly gain DNA binding specificity by forming cooperative homodimers on precisely spaced and oriented DNA sites. High-resolution genomic binding assays revealed that Gsx2 binds both monomer and homodimer sites in the developing mouse ventral telencephalon. Importantly, reporter assays showed that Gsx2 mediates opposing outcomes in a DNA binding site-dependent manner: Monomer Gsx2 binding represses transcription, whereas homodimer binding stimulates gene expression. In
Identifiants
pubmed: 33334823
pii: gad.343053.120
doi: 10.1101/gad.343053.120
pmc: PMC7778271
doi:
Substances chimiques
Drosophila Proteins
0
Gsh2 protein, mouse
0
Homeodomain Proteins
0
IND protein, Drosophila
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
157-174Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM079428
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS044080
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS069893
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM063483
Pays : United States
Informations de copyright
© 2021 Salomone et al.; Published by Cold Spring Harbor Laboratory Press.
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