Biomedical subjects

Leonie Ringrose

Publications and source records attributed to Leonie Ringrose.

6 recordsLinked to original sources

PubMed2007

Polycomb/Trithorax response elements and epigenetic memory of cell identity.

Polycomb/Trithorax group response elements (PRE/TREs) are fascinating chromosomal pieces. Just a few hundred base pairs long, these elements can remember and maintain the active or silent transcriptional state of their associated genes for many cell generations, long after the initial determining activators and repressors have disappeared. Recently, substantial progress has been made towards understanding the nuts and bolts of PRE/TRE function at the molecular level and in experimentally mapping PRE/TRE sites across whole genomes. Here we examine the insights, controversies and new questions that have been generated by this recent flood of data.

Animals↗

PubMed2006

Polycomb, trithorax and the decision to differentiate.

For stem cells, life is full of potential: they have a high capacity to proliferate and a wide choice of future identities. When they differentiate, cells leave behind this freedom and become ever more committed to a single fate. Intriguingly, the Polycomb and Trithorax groups of proteins are vital to the very different natures of both stem cells and differentiated cells, but little is known about how they make the transition from one cell type to the other. A recent paper(1) throws light on this mystery, showing that the Polycomb proteins dramatically change their behaviour at a crucial moment of differentiation.

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PubMed2005

Suppression of Polycomb group proteins by JNK signalling induces transdetermination in Drosophila imaginal discs.

During the regeneration of Drosophila imaginal discs, cellular identities can switch fate in a process known as transdetermination. For leg-to-wing transdetermination, the underlying mechanism involves morphogens such as Wingless that, when activated outside their normal context, induce ectopic expression of the wing-specific selector gene vestigial. Polycomb group (PcG) proteins maintain cellular fates by controlling the expression patterns of homeotic genes and other developmental regulators. Here we report that transdetermination events are coupled to PcG regulation. We show that the frequency of transdetermination is enhanced in PcG mutant flies. Downregulation of PcG function, as monitored by the reactivation of a silent PcG-regulated reporter gene, is observed in transdetermined cells. This downregulation is directly controlled by the Jun amino-terminal kinase (JNK) signalling pathway, which is activated in cells undergoing regeneration. Accordingly, transdetermination frequency is reduced in a JNK mutant background. This regulatory interaction also occurs in mammalian cells, indicating that the role of this signalling cascade in remodelling cellular fates may be conserved.

Animals↗

PubMed2004

Distinct contributions of histone H3 lysine 9 and 27 methylation to locus-specific stability of polycomb complexes.

The Polycomb group of proteins (PcG) maintains stable epigenetic silencing of over 100 genes via PcG response elements (PREs). Here we investigate the relationship between Polycomb binding, transcriptional status, and histone H3 methylation at lysine 9 (H3K9Me) and 27 (H3K27Me) for over 30 PcG targets in Drosophila. We show that H3K9Me and H3K27Me have distinct distributions at different loci. Our data show that Polycomb binding and histone methylation at the promoter do not prevent strong transcriptional activity, and indicate instead that silencing requires methylation of both PRE and promoter. In addition, we show that trimethylated H3K9 and H3K27 peptides can compete Polycomb from polytene chromosomes, with different effects at different loci, which correlate with differences in methylation status and transcriptional activity. We use mathematical modeling to examine these data, and propose that weak Polycomb-histone tail interactions enable PcG complexes to bind dynamically to chromatin, offering opportunities for regulation.

Animals↗

PubMed2004

Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins.

During the development of multicellular organisms, cells become different from one another by changing their genetic program in response to transient stimuli. Long after the stimulus is gone, "cellular memory" mechanisms enable cells to remember their chosen fate over many cell divisions. The Polycomb and Trithorax groups of proteins, respectively, work to maintain repressed or active transcription states of developmentally important genes through many rounds of cell division. Here we review current ideas on the protein and DNA components of this transcriptional memory system and how they interact dynamically with each other to orchestrate cellular memory for several hundred genes.

Animals↗

PubMed2003

Genome-wide prediction of Polycomb/Trithorax response elements in Drosophila melanogaster.

Polycomb/Trithorax response elements (PRE/TREs) maintain transcriptional decisions to ensure correct cell identity during development and differentiation. There are thought to be over 100 PRE/TREs in the Drosophila genome, but only very few have been identified due to the lack of a defining consensus sequence. Here we report the definition of sequence criteria that distinguish PRE/TREs from non-PRE/TREs. Using this approach for genome-wide PRE/TRE prediction, we identify 167 candidate PRE/TREs, which map to genes involved in development and cell proliferation. We show that candidate PRE/TREs are bound and regulated by Polycomb proteins in vivo, thus demonstrating the validity of PRE/TRE prediction. Using the larger data set thus generated, we identify three sequence motifs that are conserved in PRE/TRE sequences.

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