title: The forkhead transcription factor FOXM1 controls cell cycle-dependent gene expression through an atypical chromatin binding mechanism.
abstract: There are nearly 50 forkhead (FOX) transcription factors encoded in the human genome and, due to sharing a common DNA binding domain, they are all thought to bind to similar DNA sequences. It is therefore unclear how these transcription factors are targeted to specific chromatin regions to elicit specific biological effects. Here, we used chromatin immunoprecipitation followed by sequencing (ChIP-seq) to investigate the genome-wide chromatin binding mechanisms used by the forkhead transcription factor FOXM1. In keeping with its previous association with cell cycle control, we demonstrate that FOXM1 binds and regulates a group of genes which are mainly involved in controlling late cell cycle events in the G(2) and M phases. However, rather than being recruited through canonical RYAAAYA forkhead binding motifs, FOXM1 binding is directed via CHR (cell cycle genes homology region) elements. FOXM1 binds these elements through protein-protein interactions with the MMB transcriptional activator complex. Thus, we have uncovered a novel and unexpected mode of chromatin binding of a FOX transcription factor that allows it to specifically control cell cycle-dependent gene expression.
authors.affiliation: University of Manchester, Manchester, United Kingdom.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Müller
authors.forename: Marianne
authors.initials: M
authors.lastname: Quaas
authors.forename: Martin
authors.initials: M
authors.lastname: Fischer
authors.forename: Namshik
authors.initials: N
authors.lastname: Han
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stutchbury
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sharrocks
authors.forename: Kurt
authors.initials: K
authors.lastname: Engeland
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D003001:Cloning, Molecular; D019295:Computational Biology; D004268:DNA-Binding Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018816:Genes, cdc; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008938:Mitosis; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors