ZBED6 modulates the transcription of myogenic genes in mouse myoblast cells

PLoS One. 2014 Apr 8;9(4):e94187. doi: 10.1371/journal.pone.0094187. eCollection 2014.


ZBED6 is a recently discovered transcription factor, unique to placental mammals, that has evolved from a domesticated DNA transposon. It acts as a repressor at the IGF2 locus. Here we show that ZBED6 acts as a transcriptional modulator in mouse myoblast cells, where more than 700 genes were differentially expressed after Zbed6-silencing. The most significantly enriched GO term was muscle protein and contractile fiber, which was consistent with increased myotube formation. Twenty small nucleolar RNAs all showed increased expression after Zbed6-silencing. The co-localization of histone marks and ZBED6 binding sites and the effect of Zbed6-silencing on distribution of histone marks was evaluated by ChIP-seq analysis. There was a strong association between ZBED6 binding sites and the H3K4me3, H3K4me2 and H3K27ac modifications, which are usually found at active promoters, but no association with the repressive mark H3K27me3. Zbed6-silencing led to increased enrichment of active marks at myogenic genes, in agreement with the RNA-seq findings. We propose that ZBED6 preferentially binds to active promoters and modulates transcriptional activity without recruiting repressive histone modifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Histones / genetics
  • Histones / metabolism
  • Mice
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Myoblasts / metabolism*
  • Promoter Regions, Genetic*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcription, Genetic*


  • Histones
  • Muscle Proteins
  • Repressor Proteins
  • ZBED6 protein, mouse

Associated data

  • GEO/GSE33227
  • GEO/GSE33430
  • SRA/SRA047361

Grant support

The work was supported by grants from the Swedish Research Council and Swedish Foundation for Strategic Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.