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PDBsum entry 5yeg
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DNA binding protein
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PDB id
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5yeg
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Cell Res
27:1365-1377
(2017)
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PubMed id:
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Molecular mechanism of directional CTCF recognition of a diverse range of genomic sites.
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M.Yin,
J.Wang,
M.Wang,
X.Li,
M.Zhang,
Q.Wu,
Y.Wang.
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ABSTRACT
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CTCF, a conserved 3D genome architecture protein, determines proper genome-wide
chromatin looping interactions through directional binding to specific sequence
elements of four modules within numerous CTCF-binding sites (CBSs) by its 11
zinc fingers (ZFs). Here, we report four crystal structures of human CTCF in
complex with CBSs of the protocadherin (Pcdh) clusters. We show that directional
CTCF binding to cognate CBSs of the Pcdh enhancers and promoters is achieved
through inserting its ZF3, ZFs 4-7, and ZFs 9-11 into the major groove along
CBSs, resulting in a sequence-specific recognition of module 4, modules 3 and 2,
and module 1, respectively; and ZF8 serves as a spacer element for variable
distances between modules 1 and 2. In addition, the base contact with the
asymmetric "A" in the central position of modules 2-3, is essential
for directional recognition of the CBSs with symmetric core sequences but
lacking module 1. Furthermore, CTCF tolerates base changes at specific positions
within the degenerated CBS sequences, permitting genome-wide CTCF binding to a
diverse range of CBSs. Together, these complex structures provide important
insights into the molecular mechanisms for the directionality, diversity,
flexibility, dynamics, and conservation of multivalent CTCF binding to its
cognate sites across the entire human genome.
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');
}
}
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