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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:
 [1];  [2];  [1];  [2];  [1];  [1];  [1];  [2];  [1]
  1. Univ. of California, Santa Cruz, CA (United States)
  2. Virginia Commonwealth Univ., Richmond, VA (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC); UC Office of the President, Multicampus Research Programs and Initiatives Grant; Sandler Foundation; National Institutes of Health (NIH)
OSTI Identifier:
1357644
Grant/Contract Number:  
AC02-06CH11357; MR-15-328599; R01CA188571; R01GM34059; R01CA132685
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Cell division; Transcription; X-ray crystallography

Citation Formats

Marceau, Aimee H., Felthousen, Jessica G., Goetsch, Paul D., Iness, Audra N., Lee, Hsiau-Wei, Tripathi, Sarvind M., Strome, Susan, Litovchick, Larisa, and Rubin, Seth M. Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters. United States: N. p., 2016. Web. doi:10.1038/ncomms12301.
Marceau, Aimee H., Felthousen, Jessica G., Goetsch, Paul D., Iness, Audra N., Lee, Hsiau-Wei, Tripathi, Sarvind M., Strome, Susan, Litovchick, Larisa, & Rubin, Seth M. Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters. United States. https://doi.org/10.1038/ncomms12301
Marceau, Aimee H., Felthousen, Jessica G., Goetsch, Paul D., Iness, Audra N., Lee, Hsiau-Wei, Tripathi, Sarvind M., Strome, Susan, Litovchick, Larisa, and Rubin, Seth M. 2016. "Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters". United States. https://doi.org/10.1038/ncomms12301. https://www.osti.gov/servlets/purl/1357644.
@article{osti_1357644,
title = {Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters},
author = {Marceau, Aimee H. and Felthousen, Jessica G. and Goetsch, Paul D. and Iness, Audra N. and Lee, Hsiau-Wei and Tripathi, Sarvind M. and Strome, Susan and Litovchick, Larisa and Rubin, Seth M.},
abstractNote = {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.},
doi = {10.1038/ncomms12301},
url = {https://www.osti.gov/biblio/1357644}, journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 7,
place = {United States},
year = {Thu Jul 28 00:00:00 EDT 2016},
month = {Thu Jul 28 00:00:00 EDT 2016}
}

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Cited by: 41 works
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The role of DNA shape in protein–DNA recognition
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DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly
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Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso
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Evolutionarily Conserved Multisubunit RBL2/p130 and E2F4 Protein Complex Represses Human Cell Cycle-Dependent Genes in Quiescence
journal, May 2007


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Some C. elegans class B synthetic multivulva proteins encode a conserved LIN-35 Rb-containing complex distinct from a NuRD-like complex
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Works referencing / citing this record:

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


Nitrogen-dependent coordination of cell cycle, quiescence and TAG accumulation in Chlamydomonas
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Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis
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Changes in chromatin accessibility ensure robust cell cycle exit in terminally differentiated cells
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Cyclin D–CDK4 relieves cooperative repression of proliferation and cell cycle gene expression by DREAM and RB
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DREAM and RB cooperate to induce gene repression and cell-cycle arrest in response to p53 activation
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RB, p130 and p107 differentially repress G1/S and G2/M genes after p53 activation
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Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM
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Human papilloma virus E7 oncoprotein abrogates the p53-p21-DREAM pathway
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