Nuclear actin is required for transcription during Drosophila oogenesis

Abstract

Actin influences gene expression at multiple levels. It regulates the activity of specific transcription factors, such as myocardin-related transcription factor (MRTF), is a component of many chromatin remodelers and linked to transcription by all three RNA polymerases (Pol).However, the molecular mechanisms by which actin participates in the gene-specific vs. general transcription have remained unclear. Here we use chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in Drosophila ovaries to demonstrate that binding of actin to the Act5C gene is not dependent on the Mrtf transcription cofactor. At the genome-wide level, actin interacts with essentially all transcribed genes and co-occupies most gene promoters together with Pol II. On highly expressed genes, actin and Pol II can be found also on the gene bodies.Manipulation of nuclear transport factors for actin leads to decreased expression of egg shell genes, demonstrating the in vivo relevance of balanced nucleo-cytoplasmic shuttling of actin for transcription.

Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing

“…Beyond its roles in chromatin remodeling complexes, actin has also been linked to different steps of transcription (Fomproix and Percipalle, 2004;Hofmann et al, 2004;Kukalev et al, 2005;Obrdlik et al, 2008;Percipalle et al, 2003), and our recent genome-wide analysis indicates that actin interacts with basically all transcribed genes (Sokolova et al, 2018). In support of this, multiple proteins related to transcription from the assembly of the PIC to Pol II-mediated elongation (Jonkers and Lis, 2015) were identified as high-confidence interactions in our MS screens ( Figure 3A,B, Supplementary table 2).…”

“…These findings imply that actin could be directly involved in pre-mRNA splicing/processing. Alternatively, the co-transcriptional nature of splicing (Herzel et al, 2017), and the involvement of actin in transcription (Fomproix and Percipalle, 2004;Hofmann et al, 2004;Kukalev et al, 2005;Obrdlik et al, 2008;Percipalle et al, 2003;Philimonenko et al, 2004;Sokolova et al, 2018), may result in the detection of these RNA splicing/processing related proteins here.…”

Cytoskeletal proteins in the cell nucleus: a special nuclear actin perspective

“…The next fascinating question is whether actin function in gene expression is restricted to the gene level or it impacts the architecture of the genome, seeing the importance of actin in long-range chromosome movement. In favor of a general function of actin in genome regulation, recent chromatin immunoprecipitation and deep sequencing studies have shown that actin binds across both mammalian and Drosophila genomes (Almuzzaini et al , 2016; Sokolova et al , 2018). Indeed, in mouse embryonic fibroblasts where both β-actin alleles are disrupted, we recently discovered that heterochromatin is reorganized.…”

Nucleoskeletal regulation of transcription: Actin on MRTF

“…Mechanistically, the RanBP9 deletion leads to decreased binding of both actin and Pol II to the chorion genes, which are required for the eggshell formation. 103 The molecular mechanisms by which nuclear actin affects transcription are still largely unclear. In the future, it will be important to decipher these mechanisms in order to understand how nuclear actin dynamics impinges on both gene specific (for example MRTF/SRF and YAP/TAZ-TEAD target genes) and general transcription.…”