A Genome-wide Map of CTCF Multivalency Redefines the CTCF Code

被引：236

作者：

Nakahashi, Hirotaka ^{[1
]}

Kwon, Kyong-Rim Kieffer ^{[1
]}

Resch, Wolfgang ^{[1
]}

Vian, Laura ^{[1
]}

Dose, Marei ^{[1
]}

Stavreva, Diana ^{[3
]}

Hakim, Ofir ^{[4
]}

Pruett, Nathanael ^{[1
]}

Nelson, Steevenson ^{[1
]}

Yamane, Arito ^{[1
]}

Qian, Jason ^{[1
]}

Dubois, Wendy ^{[2
]}

Welsh, Scott ^{[5
]}

Phair, Robert D. ^{[6
]}

Pugh, B. Franklin ^{[7
]}

Lobanenkov, Victor ^{[8
]}

Hager, Gordon L. ^{[3
]}

Casellas, Rafael ^{[1
,2
]}

机构：

[1] NIAMS, Bethesda, MD 20892 USA

[2] NCI, Ctr Canc Res, Bethesda, MD 20892 USA

[3] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA

[4] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel

[5] Peconic LLC, State Coll, PA 16803 USA

[6] Integrat Bioinformat Inc, Mountain View, CA 94024 USA

[7] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA

[8] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA

来源：

CELL REPORTS | 2013年 / 3卷 / 05期

关键词：

PROTEIN-DNA INTERACTIONS; BINDING PROTEIN; ZINC FINGERS; TRANSCRIPTION; IDENTIFICATION; ORGANIZATION; PROMOTER; MEDIATE; COHESIN; SITES;

D O I：

10.1016/j.celrep.2013.04.024

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The "CTCF code" hypothesis posits that CTCF pleiotropic functions are driven by recognition of diverse sequences through combinatorial use of its 11 zinc fingers (ZFs). This model, however, is supported by in vitro binding studies of a limited number of sequences. To study CTCF multivalency in vivo, we define ZF binding requirements at similar to 50,000 genomic sites in primary lymphocytes. We find that CTCF reads sequence diversity through ZF clustering. ZFs 4-7 anchor CTCF to similar to 80% of targets containing the core motif. Nonconserved flanking sequences are recognized by ZFs 1-2 and ZFs 8-11 clusters, which also stabilize CTCF broadly. Alternatively, ZFs 9-11 associate with a second phylogenetically conserved upstream motif at similar to 15% of its sites. Individually, ZFs increase overall binding and chromatin residence time. Unexpectedly, we also uncovered a conserved downstream DNA motif that destabilizes CTCF occupancy. Thus, CTCF associates with a wide array of DNA modules via combinatorial clustering of its 11 ZFs.

引用

页码：1678 / 1689

页数：12

共 56 条

[1] The protein CTCF is required for the enhancer blocking activity of vertebrate insulators [J].