Establishment and maintenance of cell identity involves gene silencing pathways that prevent activation of genes, when and where specific sets of them must not be expressed. Lack of silencing results in noisy consequences for the organism, namely altered genetic programs and possibly cell transformation. The genes of the Polycomb group (PcG) and trithorax group (trxG) are part of a widely conserved cell memory system that prevents changes in cell identity by maintaining transcription patterns that are set in the first stages of embryonic life, throughout development and adult stages. PcG and trxG control, respectively, the repressed and active transcriptional states of several loci in the genome including developmentally regulated and cell cycle genes. Both groups encode components of multiprotein complexes that are thought to control chromatin accessibility. Thus, chromatin structure appears to contain the molecular imprint underlying this type of epigenetic inheritance. PcG proteins are thought to maintain gene silencing by locking inactive genes in a heterochromatin-like environment, thus excluding transcription activators and being incompatible with RNA synthesis. In the case of PcG chromatin, silent state of selector genes would irreversibly program determined and differentiated cells not to leave their track. Conversely, PcG silencing is the result of an equilibrium between transcriptional opposing forces that includes trxG activators and that coexist to maintain not only terminally determined states but also competence for switch. Unexpectedly, general transcription factors, RNA Polymerase complex and possibly production of non-coding RNA appear to contribute to this complex system. Thus, inactive chromatin domains often depicted as silent satellites in the genome universe, are revealing a novel scenario with a higher degree of flexibility than previously thought.
Polycomb, epigenomes and control of cell identity
2003
Abstract
Establishment and maintenance of cell identity involves gene silencing pathways that prevent activation of genes, when and where specific sets of them must not be expressed. Lack of silencing results in noisy consequences for the organism, namely altered genetic programs and possibly cell transformation. The genes of the Polycomb group (PcG) and trithorax group (trxG) are part of a widely conserved cell memory system that prevents changes in cell identity by maintaining transcription patterns that are set in the first stages of embryonic life, throughout development and adult stages. PcG and trxG control, respectively, the repressed and active transcriptional states of several loci in the genome including developmentally regulated and cell cycle genes. Both groups encode components of multiprotein complexes that are thought to control chromatin accessibility. Thus, chromatin structure appears to contain the molecular imprint underlying this type of epigenetic inheritance. PcG proteins are thought to maintain gene silencing by locking inactive genes in a heterochromatin-like environment, thus excluding transcription activators and being incompatible with RNA synthesis. In the case of PcG chromatin, silent state of selector genes would irreversibly program determined and differentiated cells not to leave their track. Conversely, PcG silencing is the result of an equilibrium between transcriptional opposing forces that includes trxG activators and that coexist to maintain not only terminally determined states but also competence for switch. Unexpectedly, general transcription factors, RNA Polymerase complex and possibly production of non-coding RNA appear to contribute to this complex system. Thus, inactive chromatin domains often depicted as silent satellites in the genome universe, are revealing a novel scenario with a higher degree of flexibility than previously thought.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
