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Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters
Aimee H Marceau1, Jessica G Felthousen2, Paul D Goetsch3
1Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
Nature Communications
|July 29, 2016
Summary
The MuvB complex
Area of Science:
- Molecular Biology
- Gene Regulation
- Structural Biology
Background:
- The MuvB complex regulates cell cycle-dependent gene expression.
- LIN54 is a DNA-binding protein within the MuvB complex, targeting cell cycle genes homology region (CHR) elements.
Purpose of the Study:
- To characterize the DNA-binding properties of LIN54.
- To elucidate the structural basis for CHR sequence recognition by LIN54.
Main Methods:
- Biochemical characterization of DNA-binding.
- X-ray crystallography to determine the structure of LIN54 bound to DNA.
- Demonstration of LIN54's role in MuvB recruitment.
Main Results:
- The CHR consensus sequence was biochemically defined as TTYRAA.
- Two tandem cysteine-rich regions in LIN54 are essential for high-affinity DNA binding.
- Crystal structure revealed tyrosine residues mediating sequence-specific DNA binding in the minor groove.
- Tyrosine-mediated DNA binding is crucial for MuvB recruitment to promoters.
Conclusions:
- LIN54 utilizes a unique tyrosine-based mechanism for CHR DNA recognition.
- MuvB may function by binding near transcription start sites and influencing nucleosome positioning.
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