KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control.

ABSTRACT: Embryonic stem (ES) cells are regulated by a network of transcription factors that maintain the pluripotent state. Differentiation relies on down-regulation of pluripotency transcription factors disrupting this network. While investigating transcriptional regulation of the pluripotency transcription factor Kruppel-like factor 4 (Klf4), we observed that homozygous deletion of distal enhancers caused a 17-fold decrease in Klf4 transcript but surprisingly decreased protein levels by less than twofold, indicating that posttranscriptional control of KLF4 protein overrides transcriptional control. The lack of sensitivity of KLF4 to transcription is due to high protein stability (half-life >24 h). This stability is context-dependent and is disrupted during differentiation, as

SUBMITTER: Dhaliwal NK 

PROVIDER: S-EPMC6672055 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature