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

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms12301· OSTI ID:1357644

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC); UC Office of the President, Multicampus Research Programs and Initiatives Grant; Sandler Foundation; National Institutes of Health (NIH)
Grant/Contract Number:
AC02-06CH11357; MR-15-328599; R01CA188571; R01GM34059; R01CA132685
OSTI ID:
1357644
Journal Information:
Nature Communications, Vol. 7, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 41 works
Citation information provided by
Web of Science

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Cited By (15)

Structural mechanism of Myb–MuvB assembly journal September 2018
RB, p130 and p107 differentially repress G1/S and G2/M genes after p53 activation journal October 2019
Nitrogen-dependent coordination of cell cycle, quiescence and TAG accumulation in Chlamydomonas journal December 2019
Cyclin D–CDK4 relieves cooperative repression of proliferation and cell cycle gene expression by DREAM and RB journal March 2019
Changes in chromatin accessibility ensure robust cell cycle exit in terminally differentiated cells journal September 2019
Cell cycle transcription control: DREAM/MuvB and RB-E2F complexes journal August 2017
Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis posted_content November 2019
Zellzykluskontrolle β-herpesviraler Kinasen text January 2021
DREAM and RB cooperate to induce gene repression and cell-cycle arrest in response to p53 activation journal August 2019
A DP-like transcription factor protein interacts with E2fl1 to regulate meiosis in Tetrahymena thermophila journal March 2018
Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM journal November 2017
Human papilloma virus E7 oncoprotein abrogates the p53-p21-DREAM pathway journal June 2017
Loss of the Caenorhabditis elegans pocket protein LIN-35 reveals MuvB's innate function as the repressor of DREAM target genes journal November 2017
Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis text January 2020
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