In vivo chromatin and transcription
Chromatin contains DNA packaged by histones, by associated proteins and RNA. The dynamic structure of chromatin modulates nuclear processes, like transcription and replication, by altering the accessibility of DNA to regulatory factors. This group aims at understanding how chromatin 3D-structure affects nuclear transactions like DNA transcription and replication.
From a reciprocal standpoint, the prototypic transcription factor NF-kB dynamically browses chromatin and interacts with cognate sites on the timescale of seconds to regulate the transcriptional inflammatory response. On the timescale of hours, NF-kB undergoes cycles of cytoplasmic-to-nuclear and nuclear-to-cytoplasmic translocations, giving rise to ‘‘oscillations’’. In turn, oscillations tune the transcriptional output. The group is now integrating short and long timescale NF-kB dynamics by mathematical modeling and systems biology approaches to a better understanding of transcriptional control in inflammation. In parallel, systems to study transcription at single cell level are being developed.
The role of nucleosome occupancy in DNA replication is also investigated.
Almeida R, Fernández-Justel JM, Santa-María C, Cadoret JC, Cano-Aroca L, Lombraña R, Herranz G, Agresti A, Gómez M. Chromatin conformation regulates the coordination between DNA replication and transcription. Nat Commun. 2018 Apr 23;9(1):1590.
Nair RR, Mazza D, Brambilla F, Gorzanelli A, Agresti A and Bianchi ME. LPS-Challenged Macrophages Release Microvesicles Coated With Histones. Front. Immunol., 27 June 2018, 9:1463.
Zambrano S, De Toma I, Piffer A, Bianchi ME, Agresti A. NF-kappaB oscillations translate into functionally related patterns of gene expression. eLife 2016; 5: e09100.
Karnavas T, Pintonello L, Agresti A, Bianchi ME. Histone content increases in differentiating embryonic stem cells. Frontiers in Physiology 2014; 5: 330.
De Toma ID, Rossetti G, Zambrano S, Bianchi ME, Agresti A. Nucleosome loss facilitates the chemotactic response of macrophages. Journal of internal medicine 2014 Nov;276(5):454-69.
Zambrano S, Bianchi ME, Agresti A. A simple model of NF-kappaB dynamics reproduces experimental observations. Journal of theoretical biology 2014 Apr 21;347:44-53
Zambrano S, Bianchi ME, Agresti A. High-Throughput Analysis of NF- kappaB Dynamics in Single Cells Reveals Basal Nuclear Localization of NF- kappaB and Spontaneous Activation of Oscillations. PloS one. 2014 Mar 4;9(3):e90104.
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, Agresti A. Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output. PLoS biology. 2011 Jun;9(6):e1001086.
Sung MH, Salvatore L, De Lorenzi R, Indrawan A, Pasparakis M, Hager GL, Bianchi ME, Agresti A. Sustained oscillations of NF-kappaB produce distinct genome scanning and gene expression profiles. PLoS One. 2009 Sep 29;4(9):e7163.
Bosisio D, Marazzi I, Agresti A, Shimizu N, Bianchi ME, Natoli G. A hyper- dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-kappaB-dependent gene activity. Embo J 2006 Feb 22; 25(4): 798–810.
Agresti A, Scaffidi P, Riva A, Caiolfa VR, Bianchi ME. GR and HMGB1 Interact Only within Chromatin and Influence Each Other's Residence Time. Mol Cell. 2005 Apr 1;18(1):109-21.
Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bacchi A, Rubartelli A, Agresti A, Bianchi ME. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. Embo J. 2003 Oct 15;22(20):5551-60.