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Structure paper

TitleNucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function.
Journal, issue, pagesNature, Vol. 580, Issue 7805, Page 669-672, Year 2020
Publish dateApr 22, 2020
AuthorsSvetlana O Dodonova / Fangjie Zhu / Christian Dienemann / Jussi Taipale / Patrick Cramer /
PubMed Abstract'Pioneer' transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming. Pioneer factors can bind nucleosomal DNA to enable gene expression from regions ...'Pioneer' transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming. Pioneer factors can bind nucleosomal DNA to enable gene expression from regions of the genome with closed chromatin. SOX2 is a prominent pioneer factor that is essential for pluripotency and self-renewal of embryonic stem cells. Here we report cryo-electron microscopy structures of the DNA-binding domains of SOX2 and its close homologue SOX11 bound to nucleosomes. The structures show that SOX factors can bind and locally distort DNA at superhelical location 2. The factors also facilitate detachment of terminal nucleosomal DNA from the histone octamer, which increases DNA accessibility. SOX-factor binding to the nucleosome can also lead to a repositioning of the N-terminal tail of histone H4 that includes residue lysine 16. We speculate that this repositioning is incompatible with higher-order nucleosome stacking, which involves contacts of the H4 tail with a neighbouring nucleosome. Our results indicate that pioneer transcription factors can use binding energy to initiate chromatin opening, and thereby facilitate nucleosome remodelling and subsequent transcription.
External linksNature / PubMed:32350470
MethodsEM (single particle) / X-ray diffraction
Resolution2.504 - 5.1 Å
Structure data

EMDB-10390, PDB-6t79:
Structure of a human nucleosome at 3.2 A resolution
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-10391, PDB-6t7a:
Structure of human Sox11 transcription factor in complex with a nucleosome
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-10392, PDB-6t7b:
Structure of human Sox2 transcription factor in complex with a nucleosome
Method: EM (single particle) / Resolution: 5.1 Å

EMDB-10393, PDB-6t7c:
Structure of two copies of human Sox11 transcription factor in complex with a nucleosome
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-10394, PDB-6t7d:
Structure of human Sox11 transcription factor in complex with a nucleosome
Method: EM (single particle) / Resolution: 4.4 Å

PDB-6t78:
Structure of human Sox11 transcription factor in complex with a short DNA fragment
Method: X-RAY DIFFRACTION / Resolution: 2.504 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsNUCLEAR PROTEIN / Sox11 / transcription factor / pioneer factor / DNA / Nucleosome / histones / Sox2

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