Identification of molecular determinants of gene-specific bursting patterns by high-throughput imaging screens.

• Tác giả: Thorkell Andresson, Ronald Holewinski, Daniel R Larson, Tom Misteli, Varun Sood
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Molecular cell , 2025
• Bộ sưu tập: NCBI
• ID: 226425

Tóm tắt

Stochastic transcriptional bursting is a universal property of active genes. While different genes exhibit distinct bursting patterns, the molecular mechanisms that govern gene-specific stochastic bursting are largely unknown. We have developed a high-throughput-imaging-based screening strategy to identify cellular factors that determine the bursting patterns of native genes in human cells. We identify protein acetylation as a prominent effector of burst frequency and burst size acting via decreasing off-times and gene-specific changes in the on-time. These effects are not correlated with promoter acetylation. Instead, we demonstrate acetylation of the Integrator complex as a key determinant of gene bursting that alters Integrator interactions with transcription elongation and RNA processing factors but without affecting pausing. Our results suggest a prominent role for non-histone acetylation of a transcription cofactors as a mechanism for modulation of bursting via a far-downstream checkpoint.