Beira Jorge V., Paro Renato (2016), The legacy of Drosophila imaginal discs, in Chromosoma
Degrauwe Nils, Schlumpf Tommy B., Janiszewska Michalina, Martin Patricia, Cauderay Alexandra, Provero Paolo, Riggi Nicolo, Suvà Mario-L., Paro Renato, Stamenkovic Ivan (2016), The RNA Binding Protein IMP2 Preserves Glioblastoma Stem Cells by Preventing let-7 Target Gene Silencing, in Cell Reports
, 15(8), 1634-1647.
Yilmaz Atilgan, Engeler Rachel, Constantinescu Simona, Kokkaliaris Konstantinos D, Dimitrakopoulos Christos, Schroeder Timm, Beerenwinkel Niko, Paro Renato (2015), Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation., in Stem cell research
, 15(3), 542-53.
Comoglio Federico, Schlumpf Tommy, Schmid Virginia, Rohs Remo, Beisel Christian, Paro Renato (2015), High-resolution profiling of Drosophila replication start sites reveals a DNA shape and chromatin signature of metazoan origins., in Cell reports
, 11(5), 821-34.
Geisler Sarah J, Paro Renato (2015), Trithorax and Polycomb group-dependent regulation: a tale of opposing activities., in Development (Cambridge, England)
, 142(17), 2876-87.
Grossniklaus Ueli, Paro Renato (2014), Transcriptional silencing by polycomb-group proteins., in Cold Spring Harbor perspectives in biology
, 6(11), 019331-019331.
Sievers Cem, Paro Renato (2013), Polycomb group protein bodybuilding: working out the routines., in Developmental cell
, 26(6), 556-8.
Developmental decisions, defining lineage-specific expression patterns, need to be preserved during cell division. To this purpose, chromatin represents a major level of control Two groups of chromatin proteins are responsible for maintaining the differential gene expression patterns characterizing the individual cell types. The Polycomb group (PcG) proteins are required for a stable and heritable silencing of target genes. Conversely, the proteins of the Trithorax group (TrxG) counteract PcG repression and maintain the active expression state. Signals restricted in space and time initiate developmental choices, which are then subsequently maintained by the PcG/TrxG controlled chromatin functions. Hence, the interplay between these chromatin regulators utilizes epigenetic features and forms the molecular basis for the process of transcriptional memory. A major site of action for these epigenetic regulators is at promoters of target genes, in particular at promoters with a paused polymerase. PcG protein complexes place and bind histone modifications at repressed target genes, resulting in a reduced accessibility of the nucleosomal structure and in an inhibition of the transcriptional elongation process. The counteracting TrxG proteins exhibit functions, which open nucleosomal structures and allow the transcriptional machinery to enter processivity. Our understanding of transcriptional memory stems primarily from the involvement of the PcG and TrxG in maintaining developmental decisions. Here we would like to expand the view by analyzing whether environmentally induced stress conditions can impose epigenetically heritable gene expression states. We will used cellular systems inducible by environmental stimuli and combine new methodologies, like GRO-seq and PAR-CLIP, to study the dynamic behavior of PcG and TrxG proteins at target promoters and identify the crosstalk between the two groups at the transition from silenced to activated state. This will include the identification and functional analysis of non-coding RNAs found as important companions of PcG-induced repression. We will develop transgenic reporter systems in Drosophila sensing environmental cues and measure whether stress conditions can be imprinted into chromatin and epigenetically inherited through mitosis and meiosis.This project will provide mechanistic insight of how PcG and TrxG interactions faithfully maintain gene expression states. Given the broad spectrum of assignments this particular mechanism of transcriptional memory is executing, the knowledge gained on its role in memorizing environmental signals might even have implications for clinically relevant topics like susceptibility to late-onset diseases as diabetes or cancer.