The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes.
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.
Pubmed ID: 35082292 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
Antibodies used in this publication
- Monoclonal ANTI-FLAG® M2 antibody produced in mouse (RRID:AB_262044)
- RbBP4 Antibody (RRID:AB_890631)
- Rabbit Anti-LIN9 Polyclonal Antibody, Unconjugated (RRID:AB_1269309)
- LIN54 Antibody (RRID:AB_11218173)
- RBL2 (D9T7M) Rabbit mAb (RRID:AB_2798274)
- OctA-Probe (H-5) (RRID:AB_2017593)
- Anti-Histone H3 Antibody, Unconjugated (RRID:AB_331563)
Associated grants
- Agency: NCI NIH HHS, United States
Id: F31 CA254090 - Agency: NIGMS NIH HHS, United States
Id: P30 GM138396 - Agency: NIGMS NIH HHS, United States
Id: R01 GM124148 - Agency: NIH HHS, United States
Id: S10 OD012289
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This is a list of tools and resources that we have found mentioned in this publication.
SAMTOOLS (tool)
RRID:SCR_002105
Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsFiji (tool)
RRID:SCR_002285
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsNIH 3T3 (tool)
RRID:CVCL_0594
Cell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsHCT 116 (tool)
RRID:CVCL_0291
Cell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMonoclonal ANTI-FLAG® M2 antibody produced in mouse (antibody)
RRID:AB_262044
This monoclonal targets FLAG
View all literature mentionsRabbit Anti-LIN9 Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_1269309
This polyclonal targets LIN9
View all literature mentionsRBL2 (D9T7M) Rabbit mAb (antibody)
RRID:AB_2798274
This monoclonal targets Rb-like 2
View all literature mentionsOctA-Probe (H-5) (antibody)
RRID:AB_2017593
This monoclonal targets OctA-Probe (H-5)
View all literature mentionsAnti-Histone H3 Antibody, Unconjugated (antibody)
RRID:AB_331563
This polyclonal targets Histone H3
View all literature mentions
