Chromatin profiling of dREAM and dNuRD complexes

• Applicant: Professor Dr. Alexander Brehm
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5470729

Regulation of chromatin structure is of fundamental importance during differentiation, proliferation and malignant transformation of cells. Several chromatin regulating protein complexes have been identified but we know little about how they cooperate. dREAM and dNuRD are highly conserved multisubunit protein complexes. Human homologs of dREAM and dNuRD subunits, such as the Retinoblastoma tumour suppressor pRb and the metastasis- associated proteins MTA1-3, are deregulated in cancer. In C.elegans both complexes cooperate to regulate cell fate determination during development. Both, dREAM and dNuRD are thought to repress transcription by acting on chromatin structure. Here, we propose to use novel microarray based methods (ChlP-on-chip, DamID, RNAi/microarray) to determine genome wide binding patterns and target genes of dREAM and dNuRD. We aim to identify and characterize genes coregulated by both complexes and to reveal the role of histone modification patterns in dREAM and dNuRD mediated gene repression. With this systems biology approach, we are hoping to learn how the action of different chromatin regulating complexes is orchestrated to effect the precise execution of transcriptional programmes during the development of multicellular organisms.

• DFG Programme: Research Units
• Subproject of: FOR 531: Chromatin Mediated Biological Decisions