Name: Sonia Chachra
Diploma / M.Sc degree: Anna University, Chennai, India
(April 2004)
Title: Identifcation of Interaction Partners of C/EBPß

Abstract of Research Project

Exploring the regulation of gene transcription in the cell is necessary for a detailed understanding of the molecular basis of development and disease. Regulation of gene transcription involves the interaction of DNA-binding proteins (transcription factors) with specific sequences (cis-acting elements) present in the regulatory regions of target genes. As transcription factors play key roles in regulating gene expression, the in-depth knowledge of these proteins and their mechanism of action may lead to the identification of potential new targets for therapeutic intervention. The major focus of my research is devoted to one family of important transcription factor families i.e. the CCAAT-box enhancer binding proteins (C/EBP’s), especially C/EBPß.

C/EBP family members are expressed at high levels in the myelomonocyctic lineage and participate in the regulation of macrophage and granulocyte-restricted genes. To activate transcription of the target gene C/EBPß recruits the coactivator p300; this interaction, in turn, triggers massive phosphorylation of p300. The sites of C/EBPß-inducible phosphorylation lie within the C-terminal domain of p300 and mutation of these sites substantially impairs the activity of p300 as a coactivator of C/EBPß. Phosphorylation of p300 is also triggered by other C/EBP family members as well as by various other transcription factors that interact with the C-terminal part of p300, suggesting that this novel phosphorylation mechanism may be of great relevance.

Objectives

The PhD project is centered on the analysis of the cooperation of the C/EBPß with the coactivator p300. Of particular interest is to identify the phosphorylation sites important for the interaction of p300 with C/EBPß. A second aspect of the project is to look for interacting protein and protein kinase involved in the cross talk between p300 and C/EBPß.




Sonia Chachra
eMail: Sonia Chachra