CF2 transcription factor is involved in the regulation of Mef2 RNA levels, nuclei number and muscle fiber size

PLoS One. 2017 Jun 15;12(6):e0179194. doi: 10.1371/journal.pone.0179194. eCollection 2017.

Abstract

CF2 and Mef2 influence a variety of developmental muscle processes at distinct stages of development. Nevertheless, the exact nature of the CF2-Mef2 relationship and its effects on muscle building remain yet to be resolved. Here, we explored the regulatory role of CF2 in the Drosophila embryo muscle formation. To address this question and not having proper null CF2 mutants we exploited loss or gain of function strategies to study the contribution of CF2 to Mef2 transcription regulation and to muscle formation. Our data point to CF2 as a factor involved in the regulation of muscle final size and/or the number of nuclei present in each muscle. This function is independent of its role as a Mef2 collaborative factor in the transcriptional regulation of muscle-structural genes. Although Mef2 expression patterns do not change, reductions or increases in parallel in CF2 and Mef2 transcript abundance were observed in interfered and overexpressed CF2 embryos. Since CF2 expression variations yield altered Mef2 expression levels but with correct spatio-temporal Mef2 expression patterns, it can be concluded that only the mechanism controlling expression levels is de-regulated. Here, it is proposed that CF2 regulates Mef2 expression through a Feedforward Loop circuit.

MeSH terms

  • Animals
  • Body Patterning / physiology
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / biosynthesis*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Embryo, Nonmammalian / embryology*
  • Gene Expression Regulation, Developmental / physiology
  • Muscle Development / physiology*
  • Muscles / embryology*
  • Myogenic Regulatory Factors / biosynthesis*
  • Myogenic Regulatory Factors / genetics
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Mef2 protein, Drosophila
  • Myogenic Regulatory Factors
  • RNA, Messenger
  • Transcription Factors
  • Cf2 protein, Drosophila

Grants and funding

This work was supported by Ministerio de Economia y Competitividad español (MINECO) BFU2010-19551 to MC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.