Research Projects

Aberrant gene expression through transcription defects is a common cause of human disease, including developmental defects and cancers. The pause and release step at the promoter proximal region is crucial for the expression of developmentally-regulated genes. RNA polymerase II (Pol II) is released from the promoter and paused by DSIF and NELF protein complexes. Phosphorylation of these complexes and conserved heptad repeats of Pol II leads to the dissociation of the NELF complex, promoting transcription elongation. No other mechanisms have been widely accepted in eukaryotic transcriptional regulation. This project aims to propose a novel mechanism involving the E3 ubiquitin ligase function of TRIM28, targeting NELF-E and NELF-A components of the NELF complex. This leads to the degradation of the entire NELF complex at the promoter proximal region, allowing paused Pol II to enter the productive elongation step. The transcription elongation factor ELL is hypothesized to enhance this step by increasing overall ubiquitination by TRIM28. This study has the potential to unravel a novel mechanism of transcriptional regulation, influencing the understanding of various human disease pathogenesis.