Functional and chromatin analyses of embryonic stem cell pluripotency by reversible knockdown of bivalent domain regulators

• Applicant: Professor Dr. Albrecht M. Müller (†)
• Subject Area: Cell Biology
• Term: from 2008 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 66352807

Polycomb group (PcG) proteins are chromatin modifiers involved in heritable gene repression. Two main PcG complexes have been characterized: Polycomb repressive complex 2 (PRC2) is involved in the initiation of gene silencing, whereas Polycomb repressive complex 1 (PRC1) participates in the stable maintenance of gene repression. The polycomb complex protein Bmi1 is one of the most studied PRC1 members with essential functions for embryonic development and for regulatory conditions where flexible reprogramming of cellular transcription is crucial. The relevance of Bmi1 paralogs for the establishment and maintenance of ESC pluripotency and chromatin biology has so far not been addressed. The molecular analysis of Bmi1 paralogs that are active in ESCs will improve our understanding of PRC1 function in cellular memory formation, ESC pluripotency and differentiation. We therefore propose to study the function of Bmi1 paralogs via reversible shRNA-targeted knockdown in embryonic stem cells (ESCs). This will be instrumental to generate a comprehensive picture of the functional framework of Bmi1 paralogs. We expect this analysis to provide important new insight into the regulatory circuitry of ESCs.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1356: Pluripotency and Cellular Reprogramming