Genome Biology

 

Team

Cortesi Alice, PhD student cortesi@ingm.org
Marasca Federica, Visiting PhD Student, marasca@ingm.org
Pesant Matthieu, Post Doc, pesant@ingm.org 
Salvi Marta, Undergraduate Student, salvi@ingm.org
Sinha Shruti, Post Doc, sinha@ingm.org

Scientific Background

Despite human genome composition could estimate for up to 66-69% of repetitive DNA, the functions of this fraction is still largely ignored. Nevertheless, there are emerging evidences of the peculiar role of repeats in regulating the epigenome. For instance, DNA repeats are involved in chromosome structural organization, gene regulation, genome integrity, and evolution. Moreover, a plethora of potential functions for expressed repeat regions have been assayed using data generated by the ENCODE and FANTOM consortia. These studies indicate a functional role for repetitive DNA in cell identity by means of repeat- encoded, ncRNA-mediated mechanisms, acting both in cis and in trans. Although all cells of a developing organism have the same DNA, they express different genes and transmit transcriptional patterns to daughter cells through cell division. Evidence supports the idea that basic nuclear functions (transcription, replication, DNA repair) are structurally integrated within the nucleus. The form DNA takes in the nucleus is a result of at least three prevailing components, its organization into chromatin, the linear order of coding, non coding and repetitive elements along their respective chromosomes, and the spatial localization of DNA within the nucleus. Understanding the orchestration of gene regulation, from individual regulatory sequences to global nuclear organization, has become a feasible goal with the introduction of biochemical and molecular techniques combined with advanced three-dimensional and four-dimensional (space-time) imaging approaches. Colocalization between non contiguous elements in the genome involves many different protein complexes. Among them, we are interested in Polycomb proteins, transcriptional repressors capable of maintaining silent gene states through cell division. The most characterized PcG-encoded protein complexes are Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). PcG complexes mediate gene silencing by regulating different levels of chromatin compaction, from histone mark deposition to higher order structures. Hence, PcG proteins are organized into distinct domains in the nucleus, PcG bodies, where PcG DNA targets are localized for their efficient silencing. Indeed, FISH studies together with Chromosome Conformation Capture (3C) analyses have revealed a PcG-dependent higher-order chromatin structure, conserved in mammals.

Ongoing Projects

  1. Role of DNA repetitive elements in maintaining cell identity and coordinating transcriptional programs during cellular differentiation.
  2. Epigenetic role of D4Z4 repeat in Facioscapulohumeral Dystrophy manifestation and progression.
  3. Interplay between DNA repeats and Polycomb repressive complex in cancer transformation.

Recent Publications

Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes
Elisa Cesarini, Chiara Mozzetta, Fabrizia Marullo, Francesco Gregoretti, Annagiusi Gargiulo, Marta Columbaro, Alice Cortesi, Laura Antonelli, Simona Di Pelino, Stefano Squarzoni, Daniela Palacios, Alessio Zippo, Beatrice Bodega, Gennaro Oliva, and Chiara Lanzuolo
J Cell Biol. 2015 Oct 13;6:527. doi: 10.3389/fimmu.2015.00527. eCollection 2015. Review.

Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth
Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, Rosato A, Bicciato S, Cordenonsi M, Piccolo S.
Nat Cell Biol. 2015 Sep;17(9):1218-27. doi: 10.1038/ncb3216. Epub 2015 Aug 10.

The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4.
Ranzani V, Rossetti G, Panzeri I, Arrigoni A, Bonnal RJ, Curti S, Gruarin P, Provasi E, Sugliano E, Marconi M, De Francesco R, Geginat J, Bodega B, Abrignani S, Pagani M.
Nat Immunol. 2015 Mar;16(3):318-25

Gene regulation. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.
Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drabløs F, Lennartsson A, Rönnerblad M, Hrydziuszko O, Vitezic M, Freeman TC, Alhendi AM, Arner P, Axton R, Baillie JK, Beckhouse A, Bodega B, et al.
Science. 2015 Feb 27;347(6225):1010-4.

The statistical geometry of transcriptome divergence in cell-type evolution and cancer.
Liang C; FANTOM Consortium, Forrest AR, Wagner GP.
Nat Commun. 2015 Jan 14

Repetitive elements dynamics in cell identity programming, maintenance and disease.
Bodega B, Orlando V.
Curr Opin Cell Biol. 2014 Dec;31:67-73.

A promoter level mammalian expression atlas
Forrest A, Kawaji H, Rehli M , Baillie J , de Hoon M , Haberle V, Lassmann T, Kulakovskiy I, Lizio M, Itoh M, Andersson A, Mungall C, Meehan T, Freeman T, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schaefer U, Medvedeva Y, Taylor M, Francescatto F, Vitezic M, Severin J, Semple C, Ishizu Y, Kaiho A, Saka A, Hasegawa H, Knox A, Mackay-Sim A, Edge A, Bonetti A, Diehl A, Favorov A, Meynert A, Saxena A, Joshi A, Califano A, Lennartsson A, Gibson A, Kwon A, Schwegmann A, Beckhouse A, Mathelier A, Blumenthal A, Sajantila A, Pain A, Kasianov A, Kubosaki A, Deplancke B, Bodega B, et al., [Fantom_5 Consortium].
Nature. 2014 Mar 27;507(7493):462-70.

An atlas of active enhancers across human cell types and tissues.
Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA, Jensen TH, Suzuki H, Hayashizaki Y, Müller F; FANTOM Consortium, Forrest AR, Carninci P, Rehli M, Sandelin A, Kawaji H, Baillie JK, de Hoon MJ, Haberle V, Lassmann T, Kulakovskiy IV, Lizio M, Itoh M, Andersson R, Mungall CJ, Meehan TF, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schmid C, Schaefer U, Medvedeva YA, Plessy C, Vitezic M, Severin J, Semple CA, Ishizu Y, Young RS, Francescatto M, Alam I, Albanese D, Altschuler GM, Arakawa T, Archer JA, Arner P, Babina M, Rennie S, Balwierz PJ, Beckhouse AG, Pradhan-Bhatt S, Blake JA, Blumenthal A, Bodega B, et al., [Fantom_5 Consortium].
Nature. 2014 Mar 27;507(7493):455-61

Evolutionary history of linked D4Z4 and Beta satellite clusters at the FSHD locus (4q35)
Giussani M, Cardone MF, Bodega B, Ginelli E, Meneveri R. (2012).
Genomics, 100(5):289-296.

A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy.
Cabianca DS, Casa V, Bodega B, Xynos A, Ginelli E, Tanaka Y, Gabellini D. (2012)
Cell, May 11;149(4):819-31.

Chromatin regulated interchange between PRC2-Ezh2 and PRC2- Ezh1 complexes controls Myogenin activation in skeletal muscle cells.
Stojic L, Jasencakova Z, Prezioso C, Stutzer A, Bodega B, Pasini D, Klingberg R, Mozzetta C, Margueron R, Puri PL, Schwarzer D, Helin K, Fischle W, Orlando V. (2011).
Epigenetics and Chromatin, 2011 5;4:161

Expression Profiling of FSHD-1 and FSHD-2 Cells during Myogenic Differentiation Evidences Common and Distinctive Gene Dysregulation Patterns.
Cheli S, François S, Bodega B, Ferrari F, Tenedini E, Roncaglia E, Ferrari S, Ginelli E, Meneveri R.
PLoS ONE, 2011. 6(6):e20966.

Remodelling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation.
Bodega B*, Di Capua G, Grasser F, Cheli S, Brunelli S, Mora M, Meneveri R, Marozzi A, Muller S, Battaglioli E, Ginelli E.
BMC Biology 2009. 7:41.

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