The Dynamics of Transcriptional Activation by Hepatic Reprogramming Factors.
Animals
Binding Sites
Cells, Cultured
Cellular Reprogramming
/ physiology
Chromatin
/ metabolism
DNA Polymerase II
/ genetics
Fibroblasts
/ cytology
Gene Expression Regulation
Hepatocyte Nuclear Factor 3-gamma
/ genetics
Hepatocyte Nuclear Factor 4
/ genetics
Liver
/ cytology
Mice, Inbred C57BL
Protein Domains
Transcription Initiation Site
Transcriptional Activation
RNA polymerase II
cell proliferation
direct reprogramming
gene expression
hepatocyte
liver
pioneer factor
transactivation domain
transcription factor
transcriptional activation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
20 08 2020
20 08 2020
Historique:
received:
08
04
2020
revised:
18
06
2020
accepted:
09
07
2020
pubmed:
7
8
2020
medline:
25
9
2020
entrez:
7
8
2020
Statut:
ppublish
Résumé
Specific combinations of two transcription factors (Hnf4α plus Foxa1, Foxa2, or Foxa3) can induce direct conversion of mouse fibroblasts into hepatocyte-like cells. However, the molecular mechanisms underlying hepatic reprogramming are largely unknown. Here, we show that the Foxa protein family members and Hnf4α sequentially and cooperatively bind to chromatin to activate liver-specific gene expression. Although all Foxa proteins bind to and open regions of closed chromatin as pioneer factors, Foxa3 has the unique potential of transferring from the distal to proximal regions of the transcription start site of target genes, binding RNA polymerase II, and co-traversing target genes. These distinctive characteristics of Foxa3 are essential for inducing the hepatic fate in fibroblasts. Similar functional coupling of transcription factors to RNA polymerase II may occur in other contexts whereby transcriptional activation can induce cell differentiation.
Identifiants
pubmed: 32755593
pii: S1097-2765(20)30502-5
doi: 10.1016/j.molcel.2020.07.012
pii:
doi:
Substances chimiques
Chromatin
0
Foxa3 protein, mouse
0
Hepatocyte Nuclear Factor 4
0
Hnf4a protein, mouse
0
Hepatocyte Nuclear Factor 3-gamma
135845-91-9
DNA Polymerase II
EC 2.7.7.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
660-676.e8Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.