HMGA2 links promoter-specific H2A.X deposition and active DNA demethylation [RNA-Seq]

During transcriptional activation, chromatin undergoes structural changes with the help of various proteins such as chromatin remodeling factors and histone modifiers in order to make the DNA accessible for the transcription factors and RNA polymerase. We combined ChIP-, MNase- and RNA-sequencing analyzing the Hmga2 knock-out mice and found that HMGA2 is required for promoter specific deposition of the histone variant H2A.X. Consequently, the promoter specific H2A.X deposition resulted in an accumulation of active RNA Polymerase II at these promoters. Stimulation with TGFB1 resulted in increased accumulation of pH2A.X and expression of those “primed” target genes, whereas cells expressing no Hmga2 where not able to respond. RNA-seq of Hmga2+/+ and Hmga2-/- mouse embryonic fibroblasts treated with TGFB1