Mechanisms of Disease Chromatin Structure and Function

Ferran Azorín

Group Leader

Professor (IBMB-CSIC)

ferran.azorin@irbbarcelona.org

+34 93 40 34958

Research keywords

Genomic functions take place in chromatin, not in naked DNA. In recent years, our knowledge about the regulation of chromatin functions has improved thanks to the identification of components and mechanisms that modify its structural and functional properties, such as remodelling complexes, histone modifications (acetylation, methylation...) and the corresponding enzymes, histone variants that localise to specific genomic loci, structural non-histone proteins that contribute to the structural properties of specific chromatin regions (heterochromatin), among others. Our research focuses on the study of the epigenetic mechanisms that regulate chromatin structure and function in health and disease.

Research lines

I. Centromere structure and function. We seek to determine the structural and functional properties of centromeric chromatin and its contribution to chromosome segregation and mitosis progression.

II. Linker histones H1. We study the contribution of linker histones H1 to the epigenetic regulation of chromatin structure and function during development and differentiation.

III. 3D genome structure.We study the tridimensional organization of chromatin and its role in the regulation of genome stability and function.

IV. Epigenetics of breast cancer. We study the mechanisms involved in breast cancer progression using cell lines and 3D tumor spheroids, which are able to accurately mimic some features of solid tumors. We pay particular attention to the signaling pathways, kinases, long non-coding RNAs (lncRNAs), chromatin remodeling and DNA repair machineries, and changes in 3D chromatin organization that may be involved in the regulation of key genes central to the process of cell dedifferentiation and cancer. We are also interested in understanding the molecular mechanisms by which estrogens and progesterone induce cell proliferation in breast cancer cells.

Selected publications

A fraction of barrier-to-autointegration factor (BAF) associates with centromeres and controls mitosis progression

Torras-Llort M, Medina-Giró S, Escudero-Ferruz P, Lipinszki Z, Moreno-Moreno O, Karman Z, Przewloka MR and Azorín F.

Nat Commun, 3 (1), 454 (2020)

The embryonic linker histone dBigH1 alters the functional state of active chromatin

Climent-Cantó P, Carbonell A, Tatarski M, Reina O, Bujosa P, Font-Mateu J, Bernués J, Beato M and Azorín F.

Nucleic Acids Res, (2020)

The glucocorticoid receptor interferes with progesterone receptor-dependent genomic regulation in breast cancer cells

Ogara MF, Rodríguez-Seguí SA, Marini M, Nacht AS, Stortz M, Levi V, Presman DM, Vicent GP and Pecci A.

Nucleic Acids Res, 47 (20), 10645-1066 (2019)

C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells

Nacht AS, Ferrari R, Zaurin R, Scabia V, Carbonell-Caballero J, Le Dily F, Quilez J, Leopoldi A, Brisken C, Beato M and Vicent GP.

Embo J, 38 (18), e101426 (2019)

Hormone-control regions mediate steroid receptor-dependent genome organization

Le Dily F, Vidal E, Cuartero Y, Quilez J, Nacht AS, Vicent GP, Carbonell-Caballero J, Sharma P, Villanueva-Cañas JL, Ferrari R, De Llobet LI, Verde G, Wright RHG and Beato M.

Genome Res, 29 (1), 29-39 (2019)

The E3-ligases SCFPpa and APC/CCdh1 co-operate to regulate CENP-ACID expression across the cell cycle

Moreno-Moreno O, Torras-Llort M and Azorin F.

Nucleic Acids Res, 47 (7), 3395-3406 (2019)

The Germline Linker Histone dBigH1 and the Translational Regulator Bam Form a Repressor Loop Essential for Male Germ Stem Cell Differentiation

Carbonell A, Pérez-Montero S, Climent-Cantó P, Reina O and Azorín F.

Cell Rep, 21 (11), 3178-3189 (2017)

Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin

Bayona-Feliu A, Casas-Lamesa A, Reina O, Bernués J and Azorín F.

Nat Commun, 8 (1), 283 (2017)

Variations on a nucleosome theme: The structural basis of centromere function

Moreno-Moreno O, Torras-Llort M and Azorín F.