Actin and myosin in transcription and chromatin regulation

In mammalian cells, actin and myosin have emerged as regulators of nuclear structure and function, involved in chromatin remodeling and histone modifications, and in different phases of gene transcription. Actin and myosin have also been shown to be incorporated into nascent ribonucleoprotein complexes. In the cell nucleus, actin undergoes regulated polymerization and this may be linked to yet unknown mechanisms of nuclear reprogramming. The aims of this thesis were to gain further insights into the functions of actin and myosin in transcription by RNA polymerase I and II (RNAP) and how these mechanisms are regulated. We investigated, in particular, the interplay between actin and a form of myosin 1c, termed nuclear myosin 1 (NM1), which localizes to the cell nucleus. We found that NM1 interacts with the chromatin and with actin to facilitate association of the RNAP with the gene promoter and the transcription start site. At this specific location, NM1 also promotes a chromatin state compatible with transcription activation. NM1 accomplishes this by facilitating chromatin remodeling by the WICH complex, with the subunits WSTF and SNF2h, and by promoting epigenetic reprogramming. In paper I and in paper IV, we show that these mechanisms apply to both RNAP I and RNAP II transcription activation. In paper II, we show that NM1 is regulated by GSK3β through a specific phosphorylation in the NM1 C-terminus that stabilizes the interaction of NM1 with rDNA chromatin. Finally, we show in paper III that knocking down the β-actin gene has a negative effect on transcription by RNAP I, which leads to a delay in cell cycle progression and defects in cell growth and proliferation