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Structures of CTCF–DNA complexes including all 11 zinc fingers

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkad594· OSTI ID:2470058
 [1];  [1];  [1];  [2];  [3];  [1];  [1]
  1. Univ. of Texas, Houston, TX (United States). MD Anderson Cancer Center
  2. Emory Univ., Atlanta, GA (United States). School of Medicine
  3. Univ. of Toledo, OH (United States). College of Medicine and Life Sciences
The CCCTC-binding factor (CTCF) binds tens of thousands of enhancers and promoters on mammalian chromosomes by means of its 11 tandem zinc finger (ZF) DNA-binding domain. In addition to the 12–15-bp CORE sequence, some of the CTCF binding sites contain 5' upstream and/or 3' downstream motifs. Here, we describe two structures for overlapping portions of human CTCF, respectively, including ZF1–ZF7 and ZF3–ZF11 in complex with DNA that incorporates the CORE sequence together with either 3' downstream or 5' upstream motifs. Like conventional tandem ZF array proteins, ZF1–ZF7 follow the right-handed twist of the DNA, with each finger occupying and recognizing one triplet of three base pairs in the DNA major groove. ZF8 plays a unique role, acting as a spacer across the DNA minor groove and positioning ZF9–ZF11 to make cross-strand contacts with DNA. We ascribe the difference between the two subgroups of ZF1–ZF7 and ZF8–ZF11 to residues at the two positions -6 and -5 within each finger, with small residues for ZF1–ZF7 and bulkier and polar/charged residues for ZF8–ZF11. ZF8 is also uniquely rich in basic amino acids, which allows salt bridges to DNA phosphates in the minor groove. Highly specific arginine–guanine and glutamine–adenine interactions, used to recognize G:C or A:T base pairs at conventional base-interacting positions of ZFs, also apply to the cross-strand interactions adopted by ZF9–ZF11. The differences between ZF1–ZF7 and ZF8–ZF11 can be rationalized structurally and may contribute to recognition of high-affinity CTCF binding sites.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
2470058
Journal Information:
Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 16 Vol. 51; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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