Rbf Activates the Myogenic Transcriptional Program to Promote Skeletal Muscle Differentiation

• Published in: Cell reports (Cambridge) 2019-01, Vol.26 (3), p.702-719.e6
• Main Authors: Zappia, Maria Paula, Rogers, Alice, Islam, Abul B.M.M.K., Frolov, Maxim V.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; development; differentiation; Drosophila; Drosophila Proteins - genetics; E2F; growth; muscle; Muscle Development - genetics; Muscle, Skeletal - metabolism; myogenesis; pRB; Rbf; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; transcriptional program
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.12.080

The importance of the retinoblastoma tumor suppressor protein pRB in cell cycle control is well established. However, less is known about its role in differentiation during animal development. Here, we investigated the role of Rbf, the Drosophila pRB homolog, in adult skeletal muscles. We found that the depletion of Rbf severely reduced muscle growth and altered myofibrillogenesis but only minimally affected myoblast proliferation. We identified an Rbf-dependent transcriptional program in late muscle development that is distinct from the canonical role of Rbf in cell cycle control. Unexpectedly, Rbf acts as a transcriptional activator of the myogenic and metabolic genes in the growing muscles. The genomic regions bound by Rbf contained the binding sites of several factors that genetically interacted with Rbf by modulating Rbf-dependent phenotype. Thus, our results reveal a distinctive role for Rbf as a direct activator of the myogenic transcriptional program that drives late muscle differentiation. [Display omitted] •The tumor suppressor Rbf promotes muscle growth and myofibrillogenesis•The loss of Rbf severely affects the myogenic transcriptional program•Rbf activates the transcription of myogenic genes in an E2F-dependent manner•Rbf genetically interacts with usp, ct, and Stat92E in late myogenesis Inactivation of the tumor suppressor RB, an obligatory step in most cancers, results in unrestrained cell cycle progression. Zappia et al. show that Rbf, the RB Drosophila ortholog, directly activates the metabolic program that accompanies muscle development. This work expands the understanding of the plethora of Rbf functions.