View the Current Issue

Article

  • The EMBO Journal (2003) 22, 5125 - 5136
  • doi:10.1093/emboj/cdg496

CIITA regulates transcription onset via Ser5-phosphorylation of RNA Pol II

Charalambos Spilianakis1,2,4, Androniki Kretsovali2,4, Theodora Agalioti3,4, Takis Makatounakis2, Dimitris Thanos3 and Joseph Papamatheakis1,2

  1. Department of Biology, University of Crete, Heraklion 71110, Crete
  2. Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion 71110, Crete
  3. Institute of Molecular Biology and Genetics, Biomedical Sciences Research Center 'Al. Fleming', 34 Al. Fleming Street, Vari-Athens 16602, Greece
  4. C.Spilianakis, A.Kretsovali and T.Agalioti contributed equally to this work

Correspondence to:

Joseph Papamatheakis, E-mail: papamath@imbb.forth.gr

Received 1 January 2003; Accepted 11 August 2003; Revised 22 July 2003

We describe the temporal order of recruitment of transcription factors, cofactors and basal transcriptional components and the consequent biochemical events that lead to activation of the major histocompatibility class II (MHCII) DRA gene transcription by IFN-gamma. We found that the gene is 'poised' for activation since both the activators and a fraction of the basal transcriptional machinery are pre-assembled at the enhancer and promoter prior to IFN-gamma treatment. The class II transactivator is synthesized following IFN-gamma treatment and it is recruited to the enhanceosome leading to the subsequent recruitment of the CBP and GCN5 coactivators. This is followed by histone acetylation and recruitment of the SWI/SNF chromatin remodeling complex. CIITA also recruits the CDK7 and CDK9 kinases and enhances the ability of CDK7 to phosphorylate Pol II at Ser5 leading to initiation of mRNA synthesis. Thus, the gene-specific class II transactivator selects the target genes for expression by coordinating a multiple set of biochemical activities ranging from chromatin alterations and pre-initiation complex assembly to promoter clearance.

  • Keywords:

    • chromatin immunoprecipitation,
    • CIITA,
    • enhanceosome,
    • RNA Pol II phosphorylation,
    • transcriptional regulation