Understanding the genetic basis of cancers has been a topic of intense research, and hundreds of gene mutations have been identified that can cause carcinogenesis. However, in the past few years, increasing evidence has suggested that mutations are not the only genetic changes that lead to cancer. Indeed, perturbations of chromatin structure and of other epigenetic mechanisms can cause inappropriate gene expression and genomic instability, resulting in cellular transformation and malignant outgrowth.
Our research investigation is focused on understanding the role of several protein complexes that are involved in chromatin dynamics and metabolism, which when altered could participate in the establishment and maintenance of the aberrant silencing of tumor suppressor genes during transformation. Our results suggested that the Nucleosome Remodelling and Deacetylase complex (NuRD), Polycomb group of proteins (PcG) and the histone variant macroH2A are - with different timing and kinetics - involved in setting up an altered chromatin structure with aberrant gene silencing in acute promyelocytic leukemia (APL). We believe that the results of our research will lead to the identification of new biological tools with a potential impact on cancer therapeutic intervention.

All Publications at the CRG database Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L. "The histone variant macroH2A is an epigenetic regulator of key developmental genes". Nat Struct Mol Biol. 16(10):1074-9. Epub 2009 Sep 6. (2009). PubMed ID: 19734898.abstract Cardamone MD, Bardella C, Gutierrez A, Di Croce L, Rosenfeld MG, Di Renzo MF, De Bortoli M.. ERalpha as ligand-independent activator of CDH-1 regulates determination and maintenance of epithelial morphology in breast cancer cells. Proc Natl Acad Sci U S A. 106(18): 7420–7425 (2009). PubMed ID: 19383788.abstract Morey L, Brenner C, Fazi F, Villa R, Gutierrez A, Buschbeck M, Nervi C, Minucci S, Fuks F, Di Croce L.. MBD3, a component of the NuRD complex, facilitates chromatin alteration and deposition of epigenetic marks. Mol Cell Biol. 28(19):5912-23. (2008). abstract Di Croce L, Shiekhattar R.. Thrilling transcription through threonine phosphorylation Nat Cell Biol. 10(1):5-6. (2008). abstract Lee MG, Villa R, Trojer P, Norman J, Yan KP, Reinberg D, Di Croce L, Shiekhattar R. "Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination". Science. 318(5849):447-50 (2007). abstract

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