Cellular senescence is defined as a basic aging process characterized by an irreversible growth arrest and a multi-faceted secretory phenotype (SAPS). Senescent cells have potent paracrine activities on normal and premalignant cells often inducing malignant phenotypes. Studying the behavior of senescent cells in vivo Judith Campisi showed that The SAPS can create a pro-inflammatory tissue environment that stimulates the development of cancer metastases. Thus, a better knowledge of the component of the SAPS could be beneficial to combat aging phenotypes and pathologies correlated with senescence.
The first day of the 13th CRG Symposium was focused on Chromatin Architecture & Dynamics and on the Mechanisms of Gene Regulation. The talks of some of the most influential scientists in the fields reflect that Form and Function in biology are intimately related aspects that finally can be investigated in detail. The advanced high-resolution imaging technologies, as well as recent advances in high-throughput sequencing and informatics to model and monitor genome-wide chromatin contact sites, are pushing the elucidation of the roles of genome architecture in coordinating global gene expression. Results on the spatial organization of chromatin in the nucleus at single cell resolution reflect another aspect of its dynamic nature. The understanding of the mechanisms that govern the dynamic structural and spatial organization of chromatin is providing important insights into gene regulation, development and epigenetic inheritance.Structural changes in chromatin are affected by the chemical modification of histone proteins and DNA, remodelling of nucleosomes, non-histone DNA-binding proteins and by noncoding RNAs. In this context, the RNAs molecules are obtaining an incredible interest in the gene regulation field and are now fully recognized as key regulatory players.
The first day of the 13th CRG Symposium was also the day of the success of the “poster speed presentation experiment” of the Organization. A one-minute presentation for each poster displayed in the following session resulted an excellent method to increase the curiosity and the affluence to the sessions and the best way to reflect the Dynamic in Science.
“C/EBPa induced immune cell transdifferentiation reveals two complementary macrophage enhancer pathways during hematopoiesis”. Chris Van Oevelen
It is known that over expression of one single transcription factor, C/EBPa, is sufficient to convert B cells into macrophages thus regulating the transdifferentiation towards different lineages. However, the molecular mechanisms through which cells acquire a new fate are still unclear. Chris Van Oevelen, from the Thomas Graf’s lab at CRG, showed that C/EBPa binds a class of specific enhancers into macrophages that are inactive and that, upon binding, are activated and induce a delayed up-regulation of nearby macrophage genes.
“The mRNA binding protein AUF1 controls skeletal muscle stem cell fate, linking AUF1 mutation to the development of limb girdle muscular dystrophy”. Robert J. Schneider
AU-rich elements (AREs) are known to regulate the mRNA stability and about the 16% of human mRNAs contain this element. The sequence is recognized by specific ARE binding proteins (AUBPs) as AUF1 that, when downregulated in mice, induce different developmental alterations as the reduction of skeletal muscle mass and muscle weakness. Schneider’lab results suggest that this phenotype is due to the prolonged and massive activation of satellite stem cells that could not differentiate into skeletal muscle cells.
RNA binding proteins are multifunctional factors that have a key role in the regulation of gene expression. Among them, Upstream of N-Ras (UNR) seems to be involved in mRNA regulation at the levels of translation and stability. In a tumor context, depletion of UNR modifies cancer specifics properties as growth and clonogenicity of melanoma cells. On the other hand, its over expression in primary cell cultures induces transformation. Even if many RNA targets were identified, its function is still under investigation in Fatima Gebauer’s lab.