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  Ernesto GUCCIONE  
  Lab Location: #3-06

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  Key Publications  

Adam Burton, Julius Muller, Shengjiang Tu, Pablo Padilla-Longoria, Ernesto Guccione, Maria-Elena Torres-Padilla.
Single-Cell Profiling of Epigenetic Modifiers Identifies PRDM14 as an Inducer of Cell Fate in the Mammalian Embryo
Cell Reports 2013 Oct 31. [Epub ahead of print]

Marco Bezzi, Shun Xie Teo, Julius Muller, Wei Chuen Mok, Sanjeeb Kumar Sahu, Leah A. Vardy, Zahid Q. Bonday and Ernesto Guccione
Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery
Genes and Development 2013 Sep 1.;27(17):1903-16. doi: 10.1101/gad.219899.113.

Tsai WW, Niessen S, Goebel N, Yates JR 3rd, Guccione E, Montminy M.
PRMT5 modulates the metabolic response to fasting signals.
Proc Natl Acad Sci U S A. 2013 May 28;110(22):8870-5. doi: 10.1073/pnas.1304602110. Epub 2013 May 13.PMID: 23671120

Sebastián C, Zwaans BM, Silberman DM, Gymrek M, Goren A, Zhong L, Ram O, Truelove J, Guimaraes AR, Toiber D, Cosentino C, Greenson JK, MacDonald AI, McGlynn L, Maxwell F, Edwards J, Giacosa S, Guccione E, Weissleder R, Bernstein BE, Regev A, Shiels PG, Lombard DB, Mostoslavsky R.
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism.
Cell. 2012 Dec 7;151(6):1185-99.
doi: 10.1016/j.cell.2012.10.047.

Phalke S, Mzoughi S, Bezzi M, Jennifer N, Mok WC, Low DH, Thike AA, Kuznetsov VA, Tan PH, Voorhoeve PM, Guccione E.
p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6.
Nucleic Acids Res. 2012 Oct;40(19):9534-42. doi: 10.1093/nar/gks858. Epub 2012 Sep 16.PMID:22987071

Kumpf S, Mihlan M, Goginashvili A, Grandl G, Gehart H, Godel
A, Schmidt J, Müller J, Bezzi M, Ittner A, Guccione E, Wolfrum C, Ricci R.
Hairless promotes PPARγ expression and is required for white adipogenesis.
EMBO Rep. 2012 Nov 6;13(11):1012-20. doi: 10.1038/embor.2012.133. Epub 2012 Sep 11.
Migliori V, Mapelli M, Guccione E.
On WD40 proteins: propelling our knowledge of transcriptional control?
Epigenetics. 2012 Aug;7(8):815-22. doi: 10.4161/epi.21140. Epub 2012 Jul 19. Review

Migliori V, Muller J, Phalke S, Low D, Bezzi M, Mok WC, Sahu SK, Gunaratne J, Capasso P, Bassi C,   Cecatiello V, De Marco A, Blackstock W, Kuznetsov V, Amati B, Mapelli M, and   Guccione E.
Symmetric dimethylation   of H3R2 is a newly identified histone mark that supports euchromatin   maintenance
Nature Structural and Molecular Biology, January 2012.

Migliori V, Phalke S,   Bezzi M, Guccione E.
Arginine/lysine-methyl/methyl   switches: biochemical role of histone arginine methylation in transcriptional  regulation
Epigenomics,Volume 2, Number 1,   February 2010, pp. 119-137(19)

Guccione E, Bassi C,  Casadio F, Martinato F, Cesaroni M, Schuchlautz H, Lüscher B & Amati B.
Methylation  of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive
Nature. 2007 Oct  18;449(7164):933-7

Guccione E, Martinato F,  Finocchiaro G, Luzi L, Tizzoni L, Dall’Olio V, Zardo G, Nervi C, Bernard L and  Amati B.
Myc-binding-site recognition in the  human genome is determined by chromatin context.
Nature Cell Biology. 2006  Jul;8(7):764-70. Epub 2006 Jun 11

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    Ernesto GUCCIONE

Ernesto Guccione obtained his Master's degree in Medical Biotechnology in 2000 from Bologna University and his PhD in 2004 from the International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy. He did his postdoctoral work at the European Institute of Oncology (Milan, Italy) where he studied the role of chromatin in defining c-Myc target site recognition. He also identified PRMT6, a member of the Protein Arginine MethylTransferase family, as an important enzyme in controlling transcriptional repression. During his postdoctoral training, he spent four months as an EMBO fellow in the laboratory of J.LaBaer at Harvard Institute of Proteomics. He joined IMCB in 2008 as an Assistant Professor.

    Methyltransferases in Development and Disease

Our group has a long-term interest in the function of Methyltransferases in Development and Disease.
In the lab we use a combination of approaches to study the function of Protein Arginine MethylTransferases (PRMTs) and PRDI-BF1-RIZ-homology-domain proteins (PRDMs) (Fig.1) in transcriptional and post-transcriptional regulation during development and cancer:

1. Functional screens and Target Identification and Validation:
Loss-of-function (LOF) genetic screens, using pooled shRNA libraries (Bric et al., 2009; Gargiulo et al., 2013; Kaelin, 2009; Lin et al., 2012; Mills et al., 2013; Prahallad et al., 2012), CRISPR/Cas9 libraries (Cong et al., 2013), or arrayed RNAi libraries (Chia et al., 2010) can be successfully exploited to identify genes that drive or inhibit development, cell differentiation or tumorigenesis. We believe that phenotype-driven forward genetic screens are the ideal approach to identify novel biomarkers for therapeutic decisions as well as direct targets for intervention (druggable members of the methyltransferase family of enzymes) (Richon et al., 2011) for the cure of a variety of human cancers or to instruct cell type specification.

2. Conditional Transgenic Knockout (KO) mice: Once we identify direct targets for intervention, we next aim to understand the effect of their depletion in vivo during development and tumorigenesis. To study the former, several projects in the lab have taken advantage of lineage specific deleter-strains to study deletions of selected methyltransferases in different tissues (Testis and Brain among others). For the cancer related projects we mainly take advantage of tumor-prone models such as the Eμ-Myc lymphoma model (Schmitt et al., 1999), which overexpresses the oncogenic transcription factor Myc (Guccione et al., 2006) (Martinato et al., 2008) (Guccione et al., 2007).

3. Biochemistry: All our projects aim at dissecting the biochemical mechanisms driving the in vivo phenotypes we observe upon depletion of the selected methyltransferases. We use in vitro methylation-assays, cell fractionation, in vitro protein-protein interactions and SILAC based quantitative Mass Spectrometry (Migliori et al., 2012) to answer a variety of questions.

4. Bioinformatics: a fundamental part of the work done in the lab deals with large datasets deriving from Chip-Sequencing profiles (of Transcription Factors/co-factors or Histone Post Translational Modifications), DNA methylation landscapes or RNA-Sequencing profiles of wild type or PRMT/PRDM depleted cells or tissues. We also actively collaborate with other groups both internationally and within IMCB, providing our expertise in computational biology (Beillard et al., 2012; Filipponi et al., 2013; Jachowicz et al., 2013; Tsai et al., 2013; Wang et al., 2014).