The role of translocated in liposarcoma in transcription

Transcription of RNA by all three RNA polymerases is highly regulated to ensure appropriate gene expression. While most transcription factors only affect one polymerase, a small number of cancer-related proteins have been shown to act with multiple polymerases and thus co-ordinate overall levels of transcription. TLS (translocated in liposarcoma), a protein that was originally identified in a characteristic chromosomal translocation and subsequently shown to affect a range of cellular processes, is now a member of this group. TLS stimulates RNA polymerase (RNAP) II while inhibiting RNAP III transcription. TLS represses transcription from all three types of RNAP III promoter in vitro, binds the general transcription factor TBP, and associates with RNAP III genes in vivo. Alteration of TLS protein levels in cells affected both steady state levels of RNAP III transcripts and the occupancy of TBP and RNAP III machinery at RNAP III genes.;We also used chromatin immunoprecipitation followed by a promoter microarray (ChIP-chip) to identify RNAP II genes regulated by TLS. A number of genes, corresponding to other known functions of TLS, were identified. TLS was indeed present at these genes in cells and alteration of TLS protein level affected the levels of transcripts from these genes. Taken together, these findings indicate that TLS regulates transcription by both RNAP II and III and suggest that cross-regulation between RNAPs may be important for maintaining normal cell growth.