2. Academic Validation
  3. Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters

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

  • Nat Commun. 2016 Jul 28;7:12301. doi: 10.1038/ncomms12301.
Aimee H Marceau 1,  Jessica G Felthousen 2,  Paul D Goetsch 3,  Audra N Iness 2,  Hsiau-Wei Lee 1,  Sarvind M Tripathi 1,  Susan Strome 3,  Larisa Litovchick 2,  Seth M Rubin 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
  • 2 Division of Hematology, Oncology and Palliative Care and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
  • 3 Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA.
PMID: 27465258 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.

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