{"id":20242,"date":"2026-04-08T08:34:48","date_gmt":"2026-04-08T07:34:48","guid":{"rendered":"https:\/\/cabd.es\/dr-dario-jesus-lupianez-garcia\/"},"modified":"2026-05-21T13:36:38","modified_gmt":"2026-05-21T12:36:38","slug":"dr-dario-jesus-lupianez-garcia","status":"publish","type":"page","link":"https:\/\/cabd.es\/en\/investigation\/departments\/genome-dynamics\/dr-dario-jesus-lupianez-garcia\/","title":{"rendered":"Dr Dar\u00edo Jes\u00fas Lupi\u00e1\u00f1ez Garc\u00eda"},"content":{"rendered":"

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Genome Dynamics<\/p>\n

3D Genomics<\/h1>\n

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Dr Dar\u00edo Jes\u00fas Lupi\u00e1\u00f1ez Garc\u00eda<\/h4>\n

Principal Investigator<\/p>\n

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Summary\u00a0<\/h2>\n
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How to fit 2 meters of DNA in a cell nucleus?<\/p>\n

Our laboratory is interested in this beautiful but complex question. In other words, we seek to understand gene regulation in the context of a 3D genome. Using in vivo models, we aim to decipher how cellular fate is determined and maintained and how this information is encoded in vertebrate genomes.<\/p>\n

Our methodology employs approaches to map 3D chromatin structures and regulatory elements, as well as cutting-edge genome editing technologies. This combination of methods allows us to define 3D regulatory landscapes with accuracy and assess their functionality in vivo.<\/p>\n

Our main research interests are the following:<\/p>\n

1-\u00a03D chromatin organization<\/u><\/strong><\/p>\n

To trigger gene expression, regulatory elements are physically bought into the vicinity of promoters in a process called \u201clooping\u201d. Although the process of gene transcription has been largely studied, the principles of how regulatory elements engage into loops and find their appropriate partner, often ignoring other nearby genes are still largely unknown.<\/p>\n

The study of the 3D organization of genomes though Chromosome Conformation Capture (3C) and derivatives (for a review, see\u00a0de Wit and de Laat, 2012<\/a><\/em>) revealed that these enhancer-promoter associations are usually confined within Topologically Associating Domains (TADs). These megabase sized domains represent broad DNA regions containing loci that interacting more frequently with themselves than with the rest of the genome (Dixon et al., 2012<\/a><\/em>;\u00a0Nora et al., 2012<\/a><\/em>). TADs display a high degree of overlapping with previously described regulatory landscapes where enhancers are able to exert their influence. Based on this, it was speculated that TADs represent fundamental genomic modules that facilitate regulatory elements to find their cognate promoters.<\/p>\n

We were among the first to demonstrate that TADs are biologically relevant: the disruption of their boundaries may cause these structures to intermingle, causing novel associations between otherwise segregated enhancer and promoter pairs (Lupi\u00e1\u00f1ez et al., 2015<\/a><\/em>;\u00a0Bianco et al., 2018<\/a><\/em>). Such interactions can lead result in aberrant patterns of gene expression and induce congenital malformations or cancer (Lupi\u00e1\u00f1ez et al., 2016<\/a><\/em>;\u00a0Anania et al., 2020<\/a><\/em>). Moreover, we recently showed that changes in TAD organization can also serve as a substrate for the evolution of novel phenotypes, such as the intersexuality of female moles (Real et al., 2020<\/a><\/em>) or the enlarged fins of skates (Marl\u00e9taz et al., 2023<\/a><\/em>).<\/p>\n

In ongoing projects, we seek to decipher developmental principles of 3D chromatin organization (Anania et al., 2022<\/a><\/em>) and to understand how they may have evolved (Acemel et al., 2023<\/a><\/em>)<\/p>\n

2-\u00a0Vertebrate sex determination<\/u><\/strong><\/p>\n

In vertebrates, both testes and ovaries derive from a common precursor organ:\u00a0the bipotential gonad<\/em>.<\/p>\n

In mammals, sex determination is triggered by the early expression of either SRY in the bipotential XY gonad, or its absence in the XX counterpart (for a review, see\u00a0Capel, 2017<\/a><\/em>). Upon commitment of the gonad to a specific fate, a complex genetic and hormonal cascade induces alterations on cell identity, on tissue structure and, ultimately, a series of anatomical and behavioural changes on an entire organism.<\/p>\n

Although the outcome of sex determination is conserved across species, the mechanisms of sex determination are astonishingly plastic. There is not an initiator of sex differentiation that is universal for all species. Input signals are rather variable and controlled by genetic (GSD) or environmental mechanisms (ESD), or by a combination of both. The evolutionary advantages that result from such a plastic system are still uncertain, but could be related to a certain degree of phenotypical variance within male and female categories, which may be highly adaptive in changing environments, as long as there are two compatible sexes.<\/p>\n

In ongoing projects, we aim to understand the molecular sources of the evolutionary plasticity of sex determination. For this purpose, we are profiling and comparing the process of sex determination in a wide range of vertebrate species, to identify sources of genomic and regulatory variation. We are particularly interested in evaluating the potential role of 3D chromatin organization (Mota-G\u00f3mez et al., 2022<\/a><\/em>), and on identifying novel regulators of sex determination (Hurtado et al., 2023<\/a><\/em>).<\/p>\n

 <\/p>\n

For more detailed information about our work please check out our\u00a0lab website<\/a>.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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Five relevant publications<\/h2>\n
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  1. Marl\u00e9taz F., de la Calle-Mustienes E., Acemel R.D., Paliou C., Naranjo S., Mart\u00ednez-Garc\u00eda P.M., Cases I., Sleight V.A., Hirschberger C., Marcet-Houben M., Navon D., Andrescavage A., Skvortsova K., Duckett P.E., Gonz\u00e1lez-Rajal \u00c1., Bogdanovic O., Gibcus J.H., Yang L., Gallardo-Fuentes L., Sospedra I., Lopez-Rios J., Darbellay F., Visel A., Dekker J., Shubin N., Gabald\u00f3n T., Nakamura T*., Tena J.J.*, Lupi\u00e1\u00f1ez D.G.*<\/strong>, Rokhsar D.S.*, G\u00f3mez-Skarmeta J.L*. (2023)\u00a0The little skate genome and the evolutionary emergence of wing-like fins.<\/a><\/li>\n<\/ol>\n

    Nature<\/em><\/strong>\u00a0616(7957):495-503<\/p>\n

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    1. Acemel R.D.,\u00a0Lupi\u00e1\u00f1ez D.G<\/strong>. (2023)\u00a0Evolution of 3D chromatin organization at different scales.<\/a><\/li>\n<\/ol>\n

      Curr Opin Genet Dev<\/em><\/strong>. 78:102019.<\/p>\n

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      1. Hurtado A., Mota-G\u00f3mez I., Lao M., Real F.M., Jedamzick J., Burgos M.,\u00a0Lupi\u00e1\u00f1ez D.G.*,<\/strong>\u00a0Jim\u00e9nez R.*, Barrionuevo F.J.* (2023)\u00a0Complete male-to-female sex reversal in XY mice lacking the miR-17\u223c92 cluster.<\/a><\/li>\n<\/ol>\n

        BioRxiv<\/em><\/strong>\u00a0doi: https:\/\/doi.org\/10.1101\/2023.03.22.533123<\/p>\n

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        1. Mota-G\u00f3mez I., Rodr\u00edguez J.A., Dupont S., Lao. O., Jedamzick J., K\u00fchn R., Lacadie S., Garc\u00eda-Moreno S.A., Hurtado A., Acemel R.D., Capel B.*, Marti-Renom M.*, Lupi\u00e1\u00f1ez D.G.*. (2022)\u00a0Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis.<\/a><\/li>\n<\/ol>\n

          BioRxiv<\/em><\/strong>\u00a0doi: https:\/\/doi.org\/10.1101\/2022.11.18.516861<\/p>\n

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          1. Anania, C., Acemel, R.D., Jedamzick, J., Bolondi, A., Cova, G., Brieske, N., K\u00fchn, R., Wittler, L., Real, F.M.,\u00a0Lupi\u00e1\u00f1ez D.G<\/strong>. (2022)\u00a0In vivo dissection of a clustered-CTCF domain boundary reveals developmental principles of regulatory insulation.<\/a><\/li>\n<\/ol>\n

            Nature Genetics\u00a0<\/em><\/strong>54(7):1026-1036<\/p>\n

            For a complete list of publications, click here<\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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            Lab members & collaborators<\/h2>\n
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            Lab Members<\/h3>\n

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            Principal investigator:<\/h4>\n

            Dr Dar\u00edo Lupi\u00e1\u00f1ez Garc\u00eda\u00a0<dario.lupianez@csic.es<\/a>><\/p>\n

            Postdoctoral:<\/strong><\/h4>\n

            Rafael Dominguez Acemel<\/p>\n

            Alicia Hurtado Madrid<\/p>\n

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            Collaborators<\/h3>\n

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            Kerstin Bartscherer (Osnabr\u00fcck University)<\/p>\n

            Blanche Capel (Duke University)<\/p>\n

            Lionel Christiaen (SARS Bergen)<\/p>\n

            Douglas Gibson (University of Edinburgh)<\/p>\n

            Jan Philipp Junker (MDC Berlin)<\/p>\n

            Javier L\u00f3pez Rios (CABD Sevilla)<\/p>\n

            Marc Marti-Renom (CNAG-CRG)<\/p>\n

            Philippa Saunders (University of Edinburgh)<\/p>\n

            Robert Zinzen (MDC Berlin)<\/p>\n

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