RT Journal
A1 Abaev-Schneiderman, Elina
A1 Nguyen, Linh
A1 Shalev, Raz
A1 Biton, Tzofit Elbaz
A1 Chopra, Anand
A1 Jagadeesan, Giritharan
A1 Sevilla-Sanchez, Daniel
A1 Tickotsky Moskovitz, Nili
A1 Levin, Liron
A1 Feldman, Michal
A1 Van Rechem, Capucine
A1 Levy, Dan
T1 ACTB methylation regulates SMARCA4 genomic occupancy to promote translation and reduce adhesion in colorectal cancer cells
JF Genome Research 
JO Genome Research 
YR 2026 
FD March 25 
DO 10.1101/gr.280534.125 
UL http://genome.cshlp.org/content/early/2026/03/24/gr.280534.125.abstract 
AB ACTB is a cytoskeletal protein involved in intracellular trafficking. In recent years, it has become evident that, in addition to its established roles in these compartments, ACTB also participates in the regulation of transcription. However, the molecular mechanisms underlying this function remain poorly understood. The methyltransferase SETD3 has previously been shown to methylate ACTB at H73, thereby regulating ACTB polymerization and smooth muscle contraction. Here, we show that the genomic distribution of ACTB is SETD3-dependent and that this regulation modulates the transcription of genes involved in cell adhesion and mRNA translation in colorectal cancer cells. Proteomic analyses reveal that ACTB and SETD3 interact with multiple large protein complexes, including complexes associated with transcriptional regulation. Specifically, we demonstrate that SETD3-mediated ACTB methylation is required for the colocalization of SMARCA4, a subunit of the SWI/SNF BAF complex, at specific genomic loci. Genomic analyses further show that this colocalization enables the coordinated occupancy of SMARCA4 and H73-methylated ACTB at genes involved in cell adhesion and mRNA translation. Finally, phenotypic assays confirm these regulatory effects. Together, these findings uncover a new mechanistic layer of selective transcriptional regulation mediated by an ACTB–SETD3–SMARCA4 axis in colorectal cancer cells.