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TitleStructural mechanism of synergistic targeting of the CX3CR1 nucleosome by PU.1 and C/EBPα.
Journal, issue, pagesNat Struct Mol Biol, Vol. 31, Issue 4, Page 633-643, Year 2024
Publish dateJan 24, 2024
AuthorsTengfei Lian / Ruifang Guan / Bing-Rui Zhou / Yawen Bai /
PubMed AbstractPioneer transcription factors are vital for cell fate changes. PU.1 and C/EBPα work together to regulate hematopoietic stem cell differentiation. However, how they recognize in vivo nucleosomal DNA ...Pioneer transcription factors are vital for cell fate changes. PU.1 and C/EBPα work together to regulate hematopoietic stem cell differentiation. However, how they recognize in vivo nucleosomal DNA targets remains elusive. Here we report the structures of the nucleosome containing the mouse genomic CX3CR1 enhancer DNA and its complexes with PU.1 alone and with both PU.1 and the C/EBPα DNA binding domain. Our structures reveal that PU.1 binds the DNA motif at the exit linker, shifting 17 bp of DNA into the core region through interactions with H2A, unwrapping ~20 bp of nucleosomal DNA. C/EBPα binding, aided by PU.1's repositioning, unwraps ~25 bp of entry DNA. The PU.1 Q218H mutation, linked to acute myeloid leukemia, disrupts PU.1-H2A interactions. PU.1 and C/EBPα jointly displace linker histone H1 and open the H1-condensed nucleosome array. Our study unveils how two pioneer factors can work cooperatively to open closed chromatin by altering DNA positioning in the nucleosome.
External linksNat Struct Mol Biol / PubMed:38267599
MethodsEM (single particle)
Resolution2.6 - 4.1 Å
Structure data

28629

8evh

EMDB-28629, PDB-8evh:
CX3CR1 nucleosome and wild type PU.1 complex
Method: EM (single particle) / Resolution: 2.85 Å

28630

8evi

EMDB-28630, PDB-8evi:
CX3CR1 nucleosome and PU.1 complex containing disulfide bond mutations
Method: EM (single particle) / Resolution: 2.64 Å

28631

8evj

EMDB-28631, PDB-8evj:
CX3CR1 nucleosome bound PU.1 and C/EBPa
Method: EM (single particle) / Resolution: 4.1 Å

40889

8syp

EMDB-40889, PDB-8syp:
Genomic CX3CR1 nucleosome
Method: EM (single particle) / Resolution: 2.6 Å

Source
  • homo sapiens (human)
  • escherichia coli (E. coli)
  • mus musculus (house mouse)
KeywordsTRANSCRIPTION/DNA / nucleosome / transcription factor / transcription / chromatin binding protein-DNA complex / DNA BINDING PROTEIN-DNA complex / TRANSCRIPTION-DNA complex / DNA BINDING PROTEIN

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