Identification and Functional Characterization of Polycomb Group Complexes in Drosophila
(Identificatie en Functionele Karakterisering van Polycomb Groep Complexen bij Drosophila)
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Polycomb group (PcG) and trithorax group (trxG) proteins were first discovered in Drosophila as repressors and activators of homeotic (HOX) genes, a set of transcription factors that specify cell identity along the anteroposterior axis of segmented animals. Subsequent work has shown that PcG and trxG proteins form multimeric complexes that are not required to initiate the regulation of HOX genes, but rather to maintain their expression state after the initial transcriptional regulators disappear from the embryo. The patterns of homeotic gene expression are initially set by the gap and pair-rule gene products. The early expressed gap and pair rule proteins disappear by about four hours of embryogenesis. Then, the PcG proteins maintain transcriptional repression of homeotic genes in cells where the initial expression state is off (McKeon et al., 1994; Simon et al., 1992; Struhl and Akam, 1985). In contrast, the trxG proteins maintain homeotic gene expression in cells where the initial expression state is on (reviewed in Kennison, 1993). By definition, an epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence. Epigenetic regulation of gene expression is necessary for the correct deployment of developmental programs and for the maintenance of cell fates. Since PcG proteins are responsible for the stable propagation of homeotic gene repression, after the initial decision has been made by other factors, they are referred as epigenetic regulators. Recent studies provide evidence that the PcG maintenance system regulates many other target genes in addition to homeotic genes, involved in development, cell proliferation, stem cell identity and cancer (Martinez and Cavalli, 2006; Ringrose and Paro 2004; Schwartz and Pirrotta 2007; Sparmann and van Lohuizen 2006).
The research described in this thesis was financially supported by NWO.
- dkdm 2
- prc 1
- pcg proteins
- h 2a ubiquitylation