H2A.Z is dispensable for both basal and activated transcription in post-mitotic mouse muscles [RNA-Seq - muscle]

The histone variant H2A.Z is enriched in nucleosomes surrounding the transcription start site of active promoters, suggesting that it might be implicated in transcription. It is also required during mitosis. However, evidences obtained so far mainly rely on correlative evidences obtained in actively dividing cells. We have defined a paradigm in which cell cycle cannot interfere with H2A.Z transcriptional studies by developing an in vivo systems to invalidate H2A.Z in terminally differentiated post-mitotic muscle cells to dissociate its role during transcription from its role during mitosis. ChIP-seq, RNA-seq and ATAC-seq experiments performed on H2A.Z KO post-mitotic muscle cells show that this histone variant is neither required to maintain nor to activate transcription. Altogether, this study provides in vivo evidence that in the absence of mitosis H2A.Z is dispensable for transcription and that the enrichment of H2A.Z on active promoters is rather a marker than an actor of transcriptional activity. Overall design: To address the effect of H2A.Z on both basal and activated transcription, we have used both skeletal muscle isolated from innervated and denervated control WT and H2A.Z null 7 weeks-old animals. Denervation was carried out by ablation (cutting) of the sciatic nerve of one hind mouse leg. The other hind leg (innervated) was used as a control. RNA-seq was carried out from 3 biological replicates isolated from both innervated and denervated skeletal muscles (tibialis).