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

Aimee H Marceau, Jessica G Felthousen, Paul D Goetsch, Audra N Iness, Hsiau-Wei Lee, Sarvind M Tripathi, Susan Strome, Larisa Litovchick, Seth M Rubin

Nature communications 2016 Jul 28

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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.

Citation

Aimee H Marceau, Jessica G Felthousen, Paul D Goetsch, Audra N Iness, Hsiau-Wei Lee, Sarvind M Tripathi, Susan Strome, Larisa Litovchick, Seth M Rubin. Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters. Nature communications. 2016 Jul 28;7:12301