Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence

Littler, Dene R.; Álvarez-Fernández, Mónica; Stein, Amelie; Hibbert, Richard G.; Heidebrecht, Tatjana; Aloy, Patrick; Medema, René H.; Perrakis, Anastassis

doi:10.1093/nar/gkq194

Cited by 127 publications

(115 citation statements)

References 46 publications

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“…Its forkhead DNA-binding domain (FHD) shares only 18% sequence identity with that of FoxA1, and FoxM1 has lower affinity for the forkhead consensus binding site than other Fox proteins (Littler et al, 2010). Some investigators have shown that, instead of directly interacting with the DNA of its proliferative targets, FoxM1 attaches to proteins in the DREAM complex -a larger conglomeration of proteins that prevents the transcription of proliferative targets in the quiescent state, but promotes expression of the same targets during the cell cycle (Chen et al, 2013).…”

Section: An Overview Of Fox Transcription Factorsmentioning

confidence: 99%

Fox transcription factors: from development to disease

2016

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Forkhead box (Fox) transcription factors are evolutionarily conserved in organisms ranging from yeast to humans. They regulate diverse biological processes both during development and throughout adult life. Mutations in many Fox genes are associated with human disease and, as such, various animal models have been generated to study the function of these transcription factors in mechanistic detail. In many cases, the absence of even a single Fox transcription factor is lethal. In this Primer, we provide an overview of the Fox family, highlighting several key Fox transcription factor families that are important for mammalian development.

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Section: An Overview Of Fox Transcription Factorsmentioning

confidence: 99%

Fox transcription factors: from development to disease

2016

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“…To this end, we first simulated ideal B-DNA structures containing the dimer motifs from Figure 6 using the w3DNA server (http://w3dna.rutgers.edu/). Next, we downloaded structural models from the Protein Data Bank (PDB) (Berman et al 2000) containing androgen receptor (Shaffer et al 2004) and FOX (Littler et al 2010) DNA-binding domains (PDB identifiers 1R4I and 3G73) when bound to DNA sequences that closely match the consensus of our composite motifs. Unfortunately, we found no PDB entries with reasonable sequence similarity to NFI.…”

Section: Predicted Cooperative Interactions Are Rigid and Compactmentioning

confidence: 99%

Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers

et al. 2013

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The binding of transcription factors (TFs) to their specific motifs in genomic regulatory regions is commonly studied in isolation. However, in order to elucidate the mechanisms of transcriptional regulation, it is essential to determine which TFs bind DNA cooperatively as dimers and to infer the precise nature of these interactions. So far, only a small number of such dimeric complexes are known. Here, we present an algorithm for predicting cell-type-specific TF-TF dimerization on DNA on a large scale, using DNase I hypersensitivity data from 78 human cell lines. We represented the universe of possible TF complexes by their corresponding motif complexes, and analyzed their occurrence at cell-type-specific DNase I hypersensitive sites. Based on~1.4 billion tests for motif complex enrichment, we predicted 603 highly significant celltype-specific TF dimers, the vast majority of which are novel. Our predictions included 76% (19/25) of the known dimeric complexes and showed significant overlap with an experimental database of protein-protein interactions. They were also independently supported by evolutionary conservation, as well as quantitative variation in DNase I digestion patterns. Notably, the known and predicted TF dimers were almost always highly compact and rigidly spaced, suggesting that TFs dimerize in close proximity to their partners, which results in strict constraints on the structure of the DNA-bound complex. Overall, our results indicate that chromatin openness profiles are highly predictive of cell-type-specific TF-TF interactions. Moreover, cooperative TF dimerization seems to be a widespread phenomenon, with multiple TF complexes predicted in most cell types.

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“…The lack of B-Myb binding to promoters in the absence of LIN54 and vice versa is suggestive of cooperativity that is likely dependent on both B-Myb and CHR consensus sites on promoters. In the case of FoxM1, its winged-helix domain has been reported to have a surprisingly low affinity for the consensus element TAAACA (Littler et al 2010). It is plausible that MuvB binding to its consensus sequence and to FoxM1 increases the specific affinity of FoxM1 for the late cell cycle promoters, thereby serving an essential role in recruitment of FoxM1 to the late cell cycle promoters.…”

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confidence: 99%

The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression

Sadasivam¹,

Duan²,

DeCaprio³

2012

Genes Dev.

292

428

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Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LIN37, LIN52, LIN54, and RBBP4-serves an essential role in three distinct transcription complexes to regulate cell cycle gene expression. The MuvB complex, together with the Rb-like protein p130, E2F4, and DP1, forms the DREAM complex during quiescence and represses expression of both early and late genes. Upon cell cycle entry, the MuvB complex dissociates from p130/DREAM, binds to B-Myb, and reassociates with the promoters of late genes during S phase. MuvB and B-Myb are required for the subsequent recruitment of FoxM1 to late gene promoters during G2. The MuvB complex remains bound to FoxM1 during peak late cell cycle gene expression, while B-Myb binding is lost when it undergoes phosphorylation-dependent, proteasome-mediated degradation during late S phase. Our results reveal a novel role for the MuvB complex in recruiting B-Myb and FoxM1 to promote late cell cycle gene expression and in regulating cell cycle gene expression from quiescence through mitosis.

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Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence

Cited by 127 publications

References 46 publications

Fox transcription factors: from development to disease

Fox transcription factors: from development to disease

Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers

The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression

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