A genome-wide map of CTCF multivalency redefines the CTCF code.
Cell Rep
; 3(5): 1678-1689, 2013 May 30.
Article
em En
| MEDLINE
| ID: mdl-23707059
ABSTRACT
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 â¼50,000 genomic sites in primary lymphocytes. We find that CTCF reads sequence diversity through ZF clustering. ZFs 4-7 anchor CTCF to â¼80% 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 â¼15% 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Genoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2013
Tipo de documento:
Article