Nuclear actin regulates inducible transcription by enhancing RNA polymerase II clustering

Abstract

Gene expression in response to stimuli underlies many fundamental processes. However, how transcription is regulated under these scenarios is largely unknown. Here, we find a previously unknown role of nuclear actin in transcriptional regulation. The RNA-seq data reveal that nuclear actin is required for the serum-induced transcriptional program. Using super-resolution imaging, we found a remarkable enhancement of RNA polymerase II (Pol II) clustering upon serum stimulation, and this enhancement requires nuclear actin. Pol II clusters colocalized with the serum-response genes and nuclear actin filaments upon serum stimulation. Furthermore, N-WASP is required for serum-enhanced Pol II clustering. N-WASP phase-separated with Pol II and nuclear actin. In addition to serum stimulation, nuclear actin also enhanced Pol II clustering upon interferon-γ treatment. Together, our work unveils that nuclear actin promotes the formation of transcription factory on inducible genes, acting as a general mechanism underlying the rapid response to environmental cues.

Regulation of Nuclear Mechanics and the Impact on DNA Damage

“…There is, however, growing evidence that nuclear F-actin assembly plays important roles in transcription [ 91 ], mitosis [ 92 ], DNA replication [ 93 ], DNA repair [ 94 ] and chromatin regulation [ 95 ]. Nuclear F-actin filament formation has been observed following DNA repair response (DDR) activation, caused by telomere uncapping, treatment with genotoxic drugs or UV radiation.…”

Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse

“…Emergence of tools to specifically study actin filaments in the nucleus using specific reporters with nuclear localization signals as well as the presence of filament regulators such as WASp and Arp2/3 in the nucleus have reignited interest in this field. A role for nuclear actin filaments has been described in (1) homologous repair of heterochromatic double strand breaks in Drosophila oocyte where actin nucleation via Arp2/3 generate tracks for myosins to transport heterochromatic double-strand break to the nuclear lamina ( 128 , 129 ), (2) regulating gene expression following serum starvation via N-WASp/RNA polymerase II interactions ( 130 ) and (3) in regulating the expression of key cytokines downstream of T cell receptor engagement ( 126 , 131 ).…”

A polycomb-independent role of EZH2 in TGFβ1-damaged epithelium triggers a fibrotic cascade with mesenchymal cells

“…It has been shown that remodelling of the actin cytoskeleton is a major pathway involved in TGFβ1 signalling 30 . Actin is constantly shuttled between the cytoplasm and the nucleus, where it has been shown to associate with the chromatin remodelling complex and POL2 to enhance transcriptional activity 31-33 . As transcriptional regulation were among the most enriched GO term in TGFβ1-damaged EPCs, we hypothesized that ph-EZH2 may facilitate the transcriptional process of the pro-fibrotic genes through POL2 and nuclear actin.…”