ZBED6 Modulates the Transcription of Myogenic Genes in Mouse Myoblast Cells.

Jiang, Lin; Wallerman, Ola; Younis, Shady; Rubin, Carl-Johan; Gilbert, Elizabeth R.; Sundström, Elisabeth; Ghazal, Awaisa; Zhang, Xiaolan; Wang, Li; Mikkelsen, Tarjei S.; Andersson, Göran; Andersson, Leif

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.

GENETIC transcription; MYOBLASTS; LABORATORY mice; TRANSPOSONS; GENETIC repressors; GENE expression; GENE silencing

PLoS ONE, 2014, Vol 9, Issue 4, p1

1932-6203

Academic Journal

10.1371/journal.pone.0094187