title: Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
authors.forename: Aimee H
authors.initials: AH
authors.lastname: Marceau
authors.affiliation: Division of Hematology, Oncology and Palliative Care and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: Jessica G
authors.initials: JG
authors.lastname: Felthousen
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Goetsch
authors.affiliation: Division of Hematology, Oncology and Palliative Care and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: Audra N
authors.initials: AN
authors.lastname: Iness
authors.affiliation: Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
authors.forename: Hsiau-Wei
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
authors.forename: Sarvind M
authors.initials: SM
authors.lastname: Tripathi
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Strome
authors.affiliation: Division of Hematology, Oncology and Palliative Care and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Litovchick
authors.affiliation: Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Rubin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000072417:Protein Domains; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004247:DNA; D009707:Nucleosomes; D015534:Trans-Activators; D014443:Tyrosine; C523006:LIN54 protein, human