GSE133506
Nuclear Myosin I regulates genome stability by controlling p21 gene activation through a chromatin-based mechanism
Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Here, we show NM1 has a global role in chromatin regulation and this likely impacts global transcription. High-content phenotypic profiling and transcriptional profiling by RNA-Seq on NM1 KO mouse embryonic fibroblasts show extensive chromatin alteration and differential gene expression compared to a WT condition. In particular, NM1 deletion leads to significant upregulation of genes involved in DNA damage response and cell cycle, which is further supported by increased DNA damage revealed by increased ?-H2AX foci number and proliferation rate. We found that upon DNA damage, NM1 directly regulates expression of Cdkn1A (p21) and binds to p53. NM1 recruits histone acetyl-transferase PCAF and histone methyl-transferase Set1 to p21 promoter for histone H3 acetylation and methylation, facilitating Cdkn1A gene transcription.  We propose that NM1 regulates the transcriptional response upon DNA damage and imply an involvement for NM1 in genome stability. Overall design: RNA seq of primary mouse embryonic fibroblast derived from E14 NM1 WT and KO embryos. 3 replicates for each group. Each replicate represents fibroblasts derived from three embryos.