DNA-guided transcription factor cooperativity shapes face and limb mesenchyme.
ALX factors
Coordinator
TWIST1
bHLH
cooperativity
face
homeodomain
limb
mesenchyme
neural crest
transcription factor
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
17 Jan 2024
17 Jan 2024
Historique:
received:
20
04
2023
revised:
23
10
2023
accepted:
27
12
2023
medline:
24
1
2024
pubmed:
24
1
2024
entrez:
23
1
2024
Statut:
aheadofprint
Résumé
Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest that it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how "Coordinator," a long DNA motif composed of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines the regulatory regions of embryonic face and limb mesenchyme. Coordinator guides cooperative and selective binding between the bHLH family mesenchymal regulator TWIST1 and a collective of HD factors associated with regional identities in the face and limb. TWIST1 is required for HD binding and open chromatin at Coordinator sites, whereas HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in the shared regulation of genes involved in cell-type and positional identities and ultimately shapes facial morphology and evolution.
Identifiants
pubmed: 38262408
pii: S0092-8674(23)01438-1
doi: 10.1016/j.cell.2023.12.032
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.W. is a paid scientific advisory board member at Camp4 and Paratus Sciences. J.T. has a consultancy agreement with DeepMind Technologies. J.W. is an advisory board member at Cell Press journals, including Cell, Molecular Cell, and Developmental Cell.