The Dynamics of Transcriptional Activation by Hepatic Reprogramming Factors.
Mol Cell
; 79(4): 660-676.e8, 2020 08 20.
Article
in En
| MEDLINE
| ID: mdl-32755593
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcriptional Activation
/
Hepatocyte Nuclear Factor 3-gamma
/
Hepatocyte Nuclear Factor 4
/
Liver
Limits:
Animals
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2020
Document type:
Article
Affiliation country: