FOXP1 Interacts with MyoD to Repress its Transcription and Myoblast Conversion.

ABSTRACT: Forkhead transcription factors (TFs) often dimerize outside their extensive family, whereas bHLH transcription factors typically dimerize with E12/E47. Based on structural similarities, we predicted that a member of the former, Forkhead Box P1 (FOXP1), might heterodimerize with a member of the latter, MYOD1 (MyoD). Data shown here support this hypothesis and further demonstrate the specificity of this forkhead/myogenic interaction among other myogenic regulatory factors. We found that FOXP1-MyoD heterodimerization compromises the ability of MyoD to bind to E-boxes and to transactivate E box- containing promoters. We observed that FOXP1 is required for the full ability of MyoD to convert fibroblasts into myotubules. We provide a model in which FOXP1 displaces ID and E12/E47 to repress MyoD during the proliferative phase of myoblast differentiation. These data identify FOXP1 as a hitherto unsuspected transcriptional repressor of MyoD. We suggest that isolation of paired E-box and forkhead sites within 1 turn helical spacings provides potential for cooperative interactions among heretofore distinct classes of transcription factors.

SUBMITTER: Wright WE 

PROVIDER: S-EPMC7861563 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature