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

Year: 2016

Type: article

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.

Source: Nature Communications

DOI: 10.1038/ncomms12301

Authors: 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

Institutions: University of California, Santa Cruz, Virginia Commonwealth University, VCU Massey Comprehensive Cancer Center

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: U.S. Department of Energy, Sandler Foundation, National Institutes of Health, Office of Science, Office of the President, University of California, National Cancer Institute, National Institute of General Medical Sciences, Argonne National Laboratory

OpenAlex ID: W2491621873