GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324590/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324590GEOGSEfalseSmurfs regulate mesendoderm differentiation through Smad2-dependent ubiquitination of CDK9Smurf1 and Smurf2 are HECT-domain E3 ubiquitin ligases classically characterized as negative regulators of TGF-β signaling through ubiquitination of receptors and receptor-associated Smads. Whether Smurfs also regulate transcriptional output at the level of elongation has not been addressed. Here, we show that Smurf1 and Smurf2 attenuate Smad2-driven transcription by ubiquitinating CDK9. Smurf deficiency enhances CDK9 activity, increases CDK9 occupancy immediate downstream of TSS of Smad2-target genes, promotes transcription elongation at Smad2-targeted genes, and prolongs mesendoderm gene expression during differentiation. These findings uncover a previously unrecognized mechanism linking ubiquitin-mediated regulation to transcriptional elongation control and establish Smurfs as key modulators of morphogen-dependent lineage specification.2026/09/28GSE324590GSM9579911GSM9579912GSM9579910GSM9579899GSM10039309GSM10039311GSM10039310GSM10039313GSM10039312GSM9579908GSM9579909GSM9579906GSM9579907GSM9579904GSM9579905GSM9579902GSM9579903GSM9579900GSM9579901GSM10039315GSM10039314GSM10039317GSM10039316GSM10039319GSM10039318GSM1003932034290324590Mus musculus