Unit of Functional genomics
Lab of Genetica e Biologia Cellulare
tel. +051.209.4190
fax +051.209.4149
Group Leader: Giuliano Della Valle
E-mail : giuliano.dellavalle@unibo.it
Research in progress :
- The centromere is a nucleoproteic complex that acts as an essential cis-active element of eukaryotic chromosomes, by controlling the segregation of sister chromatids during cell division. The centromere of higher eukaryotes consists of repetitive elements, spanning several mega bases of DNA, the base composition and organization of which not only differs from species to species, but even between different chromosomes of the same species. Conversely, the proteinaceous component (kinetochore) is composed of a group of proteins (CENP-A, CENP-B, CENP-C, hmis12 etc). Whether specific DNA sequences are important for the assembly of an active centromere is still an open question. In fact, while some experimental data support epigenetic mechanisms controlling centromere assembly, attempts to create human artificial chromosomes point to the alpha-satellite DNA as the key player in active centromere formation. Neocentromeres are newly formed centromeres generally derived from rearranged chromosome fragments that have separated from the original centromere and represent a gain of centromeric function of a normally euchromatic chromosomal Although they display a primary constriction and are characterized by the same set of centromere proteins found at conventional active centromeres (for example CENP-A and CENP-C), they lack typical DNA repetitive elements found in centromeric heterochromatin. The aims of this our research is the definition of the molecular mechanisms underlying the DNA/protein interactions occurring at an active centromere/kinetochore complex. Specifically three main issues will address: 1) definition and characterization of the DNA sequences involved in the formation of a human neocentromere arisen from different chromosome regions; 2) investigation of a possible species-specific role of CENP-A and CENP-C in the recognition of species-specific centromere DNAs; 3) analysis of the physical interactions between CENP-C and other kinetochore proteins, specifically CENP-A and histone H3 when assembled onto centromeric DNA.
Funding :
Patents :
-
Selected Publications :
- Capozzi O., Purgato S., Verdun di Cantogno L., Grosso E., Ciccone R., Zuffardi O., Della Valle G., Rocchi M. 2008 Evolutionary and clinical neocentromeres: two faces of the same coin? Cromosoma DOI 10.1007/s00412-008-0150-z
- Liu T., Tee A.E., Porro A., Smith S. A., Dwarte T., Liu P.Y., Iraci N., Sekyere E., Haber M., Norris M.D., Diolaiti D., Della Valle G., Perini G., Marshall G.M. 2007 Activation of tissue transglutaminase transcription by histone deacetylase inhibition: a therapeutic approach for Myc oncogenesis. Proc. Natl. Acad. Sci. USA. 104:18682-18687.
- Diolaiti D., Bernardoni R., Trazzi S., Papa A., Porro A., Bono F., Herbert J.M., Perini G., and Della Valle G. 2007 Functional cooperation between TrkA and p75NTR accelerates neuronal differentiation by increased transcription of GAP43 and p21(CIP/WAF) genes via enhancement of ERK1/2 and AP-1 activities. Exper. Cell Res. 313: 2980-2992.
- Amente S, Gargano B, Diolaiti D, Della Valle G, Lania L, Majello B. 2007 p14 (ARF) interacts with N-Myc and inhibits its transcriptional activity. FEBS Lett. 581:821-825.
- Costantini C., Weindruch R., Della Valle G. and Puglielli L. 2005 A TrkA to p75NTR molecular switch activates amyloid beta-peptide generation during aging. Biochem J. 390: 59-67.
- Perini G., Diolaiti D., Porro A., and Della Valle G. 2005 In vivo transcriptional regulation of N-myc target genes is controlled by E-box methylation. Proc. Natl. Acad. Sci. USA. 102: 12117-12123.
Postgraduate training :
- Ph.D. Program in Cellular, Molecular and Industrial Biology (Project n. 1: Physiology and Cellular Biology)
-
-
Collaborations :
- : William C. Earnshaw - Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh, Scotland, U.K
- : Andrea Musacchio - Dept. of Experimental Oncology, European Institute of Oncology, Milan, Italy.
- : Carlos Ibáñez - Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
- : Jean-Marc Herbert - Sanofi-Aventis Recherche, Toulouse, France
- : Luigi Puglielli - Department of Medicine, University of Wisconsin, Madison, USA
- : Filippo Rossi - Dept. of Pathology, University of Verona, Verona, Italy
Links :
Postgraduate training
http://www.dipartimentobiologia.it/doctoraltraining/dellavalle.asp
Associazione Italiana per la Ricerca sul Cancro
http://www.airc.it/
Myc Cancer Gene database
http://www.myccancergene.org/
Human Epigenome Consortium
http://www.epigenome.org/
European Bioinformatic Institute
http://www.ebi.ac.uk/
National Center for Biotechnology Information
http://www.ncbi.nih.gov/
Research group :
Giuliano Della Valle (Full professor)
Stefania Purgato Contrattista Regione Emilia Romagna
Monica Zoli Dottoranda
