Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters

Nat Commun. 2016 Jul 28:7:12301. doi: 10.1038/ncomms12301.

Abstract

The MuvB complex recruits transcription factors to activate or repress genes with cell cycle-dependent expression patterns. MuvB contains the DNA-binding protein LIN54, which directs the complex to promoter cell cycle genes homology region (CHR) elements. Here we characterize the DNA-binding properties of LIN54 and describe the structural basis for recognition of a CHR sequence. We biochemically define the CHR consensus as TTYRAA and determine that two tandem cysteine rich regions are required for high-affinity DNA association. A crystal structure of the LIN54 DNA-binding domain in complex with a CHR sequence reveals that sequence specificity is conferred by two tyrosine residues, which insert into the minor groove of the DNA duplex. We demonstrate that this unique tyrosine-mediated DNA binding is necessary for MuvB recruitment to target promoters. Our results suggest a model in which MuvB binds near transcription start sites and plays a role in positioning downstream nucleosomes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites / genetics
  • Cell Cycle / genetics*
  • Cell Line
  • Consensus Sequence
  • Crystallography, X-Ray
  • DNA / metabolism
  • Humans
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic*
  • Protein Binding
  • Protein Domains
  • Sequence Homology, Nucleic Acid*
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Tyrosine / metabolism

Substances

  • Lin54 protein, human
  • Nucleosomes
  • Trans-Activators
  • Tyrosine
  • DNA