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TitleStructural insights into the cooperative nucleosome recognition and chromatin opening by FOXA1 and GATA4.
Journal, issue, pagesMol Cell, Vol. 84, Issue 16, Page 3061-3079.e10, Year 2024
Publish dateAug 22, 2024
AuthorsBing-Rui Zhou / Hanqiao Feng / Furong Huang / Iris Zhu / Stephanie Portillo-Ledesma / Dan Shi / Kenneth S Zaret / Tamar Schlick / David Landsman / Qianben Wang / Yawen Bai /
PubMed AbstractMouse FOXA1 and GATA4 are prototypes of pioneer factors, initiating liver cell development by binding to the N1 nucleosome in the enhancer of the ALB1 gene. Using cryoelectron microscopy (cryo-EM), ...Mouse FOXA1 and GATA4 are prototypes of pioneer factors, initiating liver cell development by binding to the N1 nucleosome in the enhancer of the ALB1 gene. Using cryoelectron microscopy (cryo-EM), we determined the structures of the free N1 nucleosome and its complexes with FOXA1 and GATA4, both individually and in combination. We found that the DNA-binding domains of FOXA1 and GATA4 mainly recognize the linker DNA and an internal site in the nucleosome, respectively, whereas their intrinsically disordered regions interact with the acidic patch on histone H2A-H2B. FOXA1 efficiently enhances GATA4 binding by repositioning the N1 nucleosome. In vivo DNA editing and bioinformatics analyses suggest that the co-binding mode of FOXA1 and GATA4 plays important roles in regulating genes involved in liver cell functions. Our results reveal the mechanism whereby FOXA1 and GATA4 cooperatively bind to the nucleosome through nucleosome repositioning, opening chromatin by bending linker DNA and obstructing nucleosome packing.
External linksMol Cell / PubMed:39121853 / PubMed Central
MethodsEM (single particle)
Resolution2.48 - 4.1 Å
Structure data

43193

8vfx

EMDB-43193, PDB-8vfx:
Cryo-EM structure of 186bp ALBN1 nucleosome aided by scFv
Method: EM (single particle) / Resolution: 2.65 Å

43194

8vfy

EMDB-43194, PDB-8vfy:
Cryo-EM structure of FoxA1 in complex with ALBN1 nucleosome (class 1)
Method: EM (single particle) / Resolution: 2.89 Å

43195

8vfz

EMDB-43195, PDB-8vfz:
Cryo-EM structure of FoxA1 in complex with ALBN1 nucleosome (class 2)
Method: EM (single particle) / Resolution: 4.1 Å

43196

8vg0

EMDB-43196, PDB-8vg0:
Cryo-EM structure of GATA4 in complex with ALBN1 nucleosome
Method: EM (single particle) / Resolution: 3.07 Å

43197

8vg1

EMDB-43197, PDB-8vg1:
Cryo-EM structure of FoxA1 and GATA4 in complex with ALBN1 nucleosome
Method: EM (single particle) / Resolution: 2.48 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • synthetic construct (others)
KeywordsNUCLEAR PROTEIN/DNA / nucleosome / pioneer transcription factors / DNA binding proteins / transcription / chromatin / NUCLEAR PROTEIN / NUCLEAR PROTEIN-DNA complex

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