E-MEXP-403 - Transcription profiling of human Burkitts lymphoma cell lines treated with trichostatin A vs controls
Submitted on 8 August 2005, released on 7 August 2006, last updated on 3 May 2014
Histone acetylation alters the chromatin state and thus gene expression and cellular activities. In spite of various applications of Histone Deacetylase inhibitors (DACIs) their mechanism or selectivity is not fully understood. We studied the mechanism by which the DACI Trichostatin A upregulates the MHC class II DRA gene in RJ225 cells lacking CIITA. We show that TSA increases HDAC1 and 2 protein mobility and reduces their recruitment to the DRA promoter. Coordinated chromatin changes are manifested by increasing H3 K4 methylation and decreasing K9 methylation, leading to elevated RNA PolII recruitment and the onset of transcription. Gene expression profiling showed that diverse TSA responsive gene groups, including the highly upregulated the MHC class II family and the adjacent histone cluster are located in chromosome 6p21-22. A complex pattern of gene reprogramming by TSA involves immune recognition, antiviral, apoptotic and inflammatory pathways and extends the rationale for using DACIs to modulate the immune response.
transcription profiling by array, compound treatment, time series
Manolis G Gialitakis <firstname.lastname@example.org>, Androniki A Kretsovali, Antonis A Hatzopoulos, Charalampos C Spilianakis, Joerg J Mages, Joseph J Papamatheakis, Lara L Kravariti, Reinhardt R Hoffman
Specific and global gene activation by inhibition of histone deacetylation. Manolis Gialitakis; Androniki Kretsovali; Charalampos Spilianakis; Lara Kravariti; Joerg Mages; Reinhardt Hoffman; Antonis Hatzopoulos; Joseph Papamatheakis. EMBO Rep