A genome-wide map of CTCF multivalency redefines the CTCF code. Academic Article uri icon

Overview

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 ∼50,000 genomic sites in primary lymphocytes. We find that CTCF reads sequence diversity through ZF clustering. ZFs 4-7 anchor CTCF 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 ∼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.

publication date

  • May 23, 2013

Research

keywords

  • Genome
  • Repressor Proteins

Identity

PubMed Central ID

  • PMC3770538

Scopus Document Identifier

  • 84878590595

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2013.04.024

PubMed ID

  • 23707059

Additional Document Info

volume

  • 3

issue

  • 5