Transcriptional regulators ensuring specific gene expression and decision-making at high TGFβ doses.

ABSTRACT: TGFβ-signaling regulates cancer progression by controlling cell division, migration, and death. These outcomes are mediated by gene expression changes, but the mechanisms of decision-making toward specific fates remain unclear. Here, we combine SMAD transcription factor imaging, genome-wide RNA sequencing, and morphological assays to quantitatively link signaling, gene expression, and fate decisions in mammary epithelial cells. Fitting genome-wide kinetic models to our time-resolved data, we find that most of the TGFβ target genes can be explained as direct targets of SMAD transcription factors, whereas the remainder show signs of complex regulation, involving delayed regulation and strong amplification at high TGFβ doses. Knockdown experiments followed by global RNA sequencing revealed tr

SUBMITTER: Hartmann L 

PROVIDER: S-EPMC11565188 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature