Chromatin dynamics Unit studies the organization and function of chromatin, and how chromatin or its components become themselves a signal when they are outside the cell.
Outside the cell, chromatin or its components act as Damage Associated Molecular Patterns (DAMP), and trigger inflammatory responses. In particular, HMGB1 (High Mobility Group Box 1) protein contributes to organize chromatin within the nucleus, and cells missing HMGB1 have fewer nucleosomes. Cells that die in an unscheduled way release HMGB1, which functions as a DAMP, binds to sevral different receptors, and warns other cells in the organism that a cell has died. HMGB1 can also be secreted actively by severely stressed cells, which at the same time alter the state of their chromatin. HMGB1 may or may not contain a disulfide bridge between two cysteines, and the two forms act on different receptors.
Recently, we have also shown that the state of tissue inflammation modulates the proportion of reduced and disulfide HMB1, and that the reduced protein promotes the repair and regeneration of damaged tissues.
De Leo F, Rossi A, De Marchis F, Cigana C, Melessike M, Quilici G, De Fino, Mantonico MV, Fabris C, Bragonzi A*, Bianchi ME* and Musco G* (*equal contribution). Pamoic acid is an inhibitor of HMGB1•CXCL12 elicited chemotaxis and reduces inflammation in murine models of Pseudomonas aeruginosa pneumonia. Mol Med. 2022;28:108. doi: 10.1186/s10020-022-00535-z PMID: 36071400
Kizilirmak C, Bianchi ME* and Zambrano S* (*equal contribution). Insights on the NF-kB system using live cell imaging: recent developments and future perspectives. Front Immunol. 2022;13: 886127. doi: 10.3389/fimmu.2022.886127 PMID: 35844496
Mezzapelle R, De Marchis F, Passera C, Leo M, Brambilla F, Colombo F, Casalgrandi M, Preti A, Zambrano S, Castellani P, Ertassi R, Silingardi M, Caprioglio F, Basso V, Boldorini R, Carretta A, Sanvito F, Rena O, Rubartelli A, Sabatino L, Mondino A, Crippa MP, Colantuoni V, Bianchi ME. CXCR4 engagement triggers CD47 internalization and antitumor immunization in a mouse model of mesothelioma. EMBO Mol Med. 2021 Jun 7;13(6):e12344. doi: 10.15252/emmm.202012344. Epub 2021 May 6. PMID: 33956406; PMCID: PMC8185548.
Francesca Brambilla, Jose Manuel Garcia-Manteiga, Emanuele Monteleone, Lena Hoelzen, Angelica Zocchi, Alessandra Agresti, Marco E Bianchi, Nucleosomes effectively shield DNA from radiation damage in living cells, Nucleic Acids Research, Volume 48, Issue 16, 18 September 2020, 8993–9006.
Tirone M, Tran NL, Ceriotti C, Gorzanelli A, Canepari M, Bottinelli R, Raucci A, Di Maggio S, Santiago C, Mellado M, Saclier M, François S, Careccia G, He M, De Marchis F, Conti V, Ben Larbi S, Cuvellier S, Casalgrandi M, Preti A, Chazaud B, Al-Abed Y, Messina G, Sitia G, Brunelli S, Bianchi ME* and Vénéreau E*. High Mobility Group Box 1 orchestrates tissue regeneration via CXCR4. J Exp Med. 2018. 215: 303-18 (*equal contribution)
Stark K, Philippi V, Stockhausen S, Busse J, Antonelli A, Miller M, Schubert I, Hoseinpour P, Chandraratne S, von Brühl M-L, Gärtner F, Lorenz M, Agresti A, Coletti R, Antoine D, Heermann R, Jung K, Reese S, Laitinen I, Schwaiger M, Walch A, Sperandio M, Nawroth P, Reinhardt C, Jäckel S, Bianchi ME* and Massberg S*. Disulfide HMGB1 derived from platelets coordinates venous thrombosis in mice. Blood. 2016. 128:2435-49 (*equal contribution)
Venereau E, Casalgrandi M, Schiraldi M, Antoine DJ, Cattaneo A, De Marchis F, Liu J, Antonelli A, Preti A, Raeli L, Samadi Shams S, Yang H, Varani L, Andersson U, Tracey KJ, Bachi A, Uguccioni M and Bianchi ME. Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release. J Exp Med. 2012. 209: 1519-28
Celona B, Weiner A, Di Felice F, Mancuso FM, Cesarini E, Rossi RL, Gregory L, Baban D, Rossetti G, Grianti P, Pagani M, Bonaldi T, Ragoussis J, Friedman N, Camilloni G, Bianchi ME* and Agresti A*. Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output. PLoS Biol. 2011. 9: e1001086 (*co-corresponding)
Palumbo R, Sampaolesi M, De Marchis F, Tonlorenzi R, Colombetti S, Mondino A, Cossu G and Bianchi ME. Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation. J Cell Biol. 2004.164: 441-9
Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, Rubartelli A, Agresti A and Bianchi ME. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO. 2003. 22: 5551-60
Scaffidi P, Misteli T and Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002. 418: 191-5
Calogero S, Grassi F, Aguzzi A, Voigtländer T, Ferrier P, Ferrari S and Bianchi ME. The lack of chromosomal protein HMG1 does not disrupt cell growth, but causes lethal hypoglycaemia in newborn mice. Nature Genet. 1999. 22: 276-80.
Bianchi ME, Beltrame M and Paonessa G. Specific recognition of cruciform DNA by nuclear protein HMG1. Science. 1989. 243: 1056-9 (Selected as a Classic by Science).
Bianchi ME and Radding CM. Insertions, deletions and mismatches in hetero-duplex DNA made by recA protein. Cell. 1983. 35: 511-20.