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

Author

Listed:
  • Aimee H. Marceau

    (University of California)

  • Jessica G. Felthousen

    (Oncology and Palliative Care and Massey Cancer Center, Virginia Commonwealth University)

  • Paul D. Goetsch

    (Cell and Developmental Biology, University of California)

  • Audra N. Iness

    (Oncology and Palliative Care and Massey Cancer Center, Virginia Commonwealth University)

  • Hsiau-Wei Lee

    (University of California)

  • Sarvind M. Tripathi

    (University of California)

  • Susan Strome

    (Cell and Developmental Biology, University of California)

  • Larisa Litovchick

    (Oncology and Palliative Care and Massey Cancer Center, Virginia Commonwealth University)

  • Seth M. Rubin

    (University of California)

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.

Suggested 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, 2016. "Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12301
    DOI: 10.1038/ncomms12301
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    Cited by:

    1. Marios G. Koliopoulos & Reyhan Muhammad & Theodoros I. Roumeliotis & Fabienne Beuron & Jyoti S. Choudhary & Claudio Alfieri, 2022. "Structure of a nucleosome-bound MuvB transcription factor complex reveals DNA remodelling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Alison K. Barrett & Manisha R. Shingare & Andreas Rechtsteiner & Kelsie M. Rodriguez & Quynh N. Le & Tilini U. Wijeratne & Corbin E. Mitchell & Miles W. Membreno & Seth M. Rubin & Gerd A. Müller, 2024. "HDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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