The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes
| Autor: | Keelan Z. Guiley, Haritha Narasimhan, Anushweta Asthana, Hinrich Boeger, Robert Shelansky, Sarvind Tripathi, Alexander Hirschi, Tilini U. Wijeratne, Michael J. Doody, Parameshwaran Ramanan, Gerd A Mueller, Seth M. Rubin |
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| Rok vydání: | 2022 |
| Předmět: |
Scaffold protein
Cell division Consensus site 1.1 Normal biological development and functioning Science General Physics and Astronomy Cell Cycle Proteins Article General Biochemistry Genetics and Molecular Biology Promoter Regions chemistry.chemical_compound Genetic Underpinning research Genetics Nucleosome cdc Promoter Regions Genetic Transcription factor Histone binding Multidisciplinary Chemistry Cell Cycle Promoter DNA General Chemistry Chromatin Nucleosomes Cell biology Genes cdc Genes Generic health relevance Transcription Initiation Site Structural biology Transcription Cell Division Biotechnology Protein Binding Transcription Factors |
| Zdroj: | Nature Communications, Vol 13, Iss 1, Pp 1-15 (2022) Nature Communications Nature communications, vol 13, iss 1 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-022-28094-1 |
| Popis: | The chromatin architecture in promoters is thought to regulate gene expression, but it remains uncertain how most transcription factors (TFs) impact nucleosome position. The MuvB TF complex regulates cell-cycle dependent gene-expression and is critical for differentiation and proliferation during development and cancer. MuvB can both positively and negatively regulate expression, but the structure of MuvB and its biochemical function are poorly understood. Here we determine the overall architecture of MuvB assembly and the crystal structure of a subcomplex critical for MuvB function in gene repression. We find that the MuvB subunits LIN9 and LIN37 function as scaffolding proteins that arrange the other subunits LIN52, LIN54 and RBAP48 for TF, DNA, and histone binding, respectively. Biochemical and structural data demonstrate that MuvB binds nucleosomes through an interface that is distinct from LIN54-DNA consensus site recognition and that MuvB increases nucleosome occupancy in a reconstituted promoter. We find in arrested cells that MuvB primarily associates with a tightly positioned +1 nucleosome near the transcription start site (TSS) of MuvB-regulated genes. These results support a model that MuvB binds and stabilizes nucleosomes just downstream of the TSS on its target promoters to repress gene expression. The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression. |
| Databáze: | OpenAIRE |
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