Lines of investigation
Chromatin three-dimensional organization within the nucleus of eukaryotic cells plays a crucial role in transcriptional regulation, allowing physical interaction between distal regulatory elements and protein-coding genes. We know that, during development, cell precursors differentiate into highly specialized cells in a process accompanied by a complex spatial reorganization of chromatin. In neuronal cells, this configuration must be maintained during their long post-mitotic life, but also presents a great level of dynamism, allowing neurons to accommodate transcriptional processes necessary to generate responses to external stimuli and give rise to the generation of memory traces that will last over time. Although in recent decades we have made significant progress in understanding some of the mechanisms involved in this spatial organization, we still know relatively little about the importance of these mechanisms in many physiological and pathological processes taking place in the nervous system.
Our aim is to better understand the key role played by the different elements involved in the spatial organization of chromatin within the nervous system, focusing on processes as relevant as the cell identity, the memory, the behavior or neurodegenerative diseases.
To this end, our group uses a wide variety of genetic tools designed to study and modulate molecular mechanisms in cellular systems, but also in murine models to study their implications in memory and behavior. Our methodology is highly multidisciplinary, combining molecular biology approaches (generation of genetic constructs and production of neurotropic vectors), next generation sequencing techniques (RNA-seq, ATAC-seq, CUT&TAG, ChIP-seq), techniques for the study of chromatin three-dimensional architecture (4C-seq, GAM) and behavioral neuroscience.
Representative Publications
- Keep calm and carry H3K27me1 off. Alcalá-Vida R, Barco A. Neuron 2024 112(17): 2829-2832 https://doi.org/10.1016/j.neuron.2024.07.014
- Dysregulated expression of cholesterol biosynthetic genes in Alzheimer’s disease alters epigenomic signatures of hippocampal neurons. Paiva I, Seguin J, Grgurina I, Singh AK, Cosquer B, Plassard D, Tzeplaeff L, Le Gras S, Cotellessa L, Decraene C, Gambi J, Alcala-Vida R, Eswaramoorthy M, Buée L, Cassel JC, Giacobini P, Blum D, Merienne K, Kundu TK, Boutillier AL. Neurobiol Dis. 2024 198: 106538 https://doi.org/10.1016/j.nbd.2024.106538
- Mutant FUS induces chromatin reorganization in the hippocampus and alters memory processes. Tzeplaeff L, Seguin J, Le Gras S, Megat S, Cosquer B, Plassard D, Dieterlé S, Paiva I, Picchiarelli G, Decraene C, Alcala-Vida R, Cassel JC, Merienne K, Dupuis L, Boutillier AL. Prog Neurobiol. 2023 227: 102483 https://doi.org/10.1016/j.pneurobio.2023.102483
- Altered activity-regulated H3K9 acetylation at TGF-beta signaling genes during egocentric memory in Huntington’s disease. Alcalá-Vida R, Lotz C, Brulé B, Seguin J, Decraene C, Awada A, Bombardier A, Cosquer B, Pereira de Vasconcelos A, Brouillet E, Cassel JC, Boutillier AL, Merienne K. Prog Neurobiol. 2022 219: 102363 https://doi.org/10.1016/j.pneurobio.2022.102363
- Altered m6A RNA methylation contributes to hippocampal memory deficits in Huntington’s disease mice. Pupak A, Singh A, Sancho-Balsells A, Alcalá-Vida R, Espina M, Giralt A, Martí E, Ørom UAV, Ginés S, Brito V. Cell Mol Life Sci. 2022 79(8): 416 https://doi.org/10.1007/s00018-022-04444-6
- Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats. De Sa Nogueira D, Bourdy R, Alcala-Vida R, Filliol D, Andry V, Goumon Y, Zwiller J, Romieu P, Merienne K, Olmstead MC, Befort K. Mol Neurobiol. 2022 59(3): 1896-1911 https://doi.org/10.1007/s12035-022-02722-9
- Age-related and disease locus-specific mechanisms contribute to early remodelling of chromatin structure in Huntington’s disease mice. Alcalá-Vida R, Seguin J, Lotz C, Molitor AM, Irastorza-Azcarate I, Awada A, Karasu N, Bombardier A, Cosquer B, Skarmeta JLG, Cassel JC, Boutillier AL, Sexton T, Merienne K. Nat Commun. 2021 12(1): 364 https://doi.org/10.1038/s41467-020-20605-2
- Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington’s disease. Alcalá-Vida R, Garcia-Forn M, Castany-Pladevall C, Creus-Muncunill J, Ito Y, Blanco E, Golbano A, Crespí-Vázquez K, Parry A, Slater G, Samarajiwa S, Peiró S, Di Croce L, Narita M, Pérez-Navarro E. EMBO Mol Med. 2021 13(2): e12105 https://doi.org/10.15252/emmm.202012105
- Epigenetic mechanisms underlying enhancer modulation of neuronal identity, neuronal activity and neurodegeneration. Alcalà-Vida R, Awada A, Boutillier AL, Merienne K. Neurobiol Dis. 2021 147: 105155 https://doi.org/10.1016/j.nbd.2020.105155
- Increased Levels of Rictor Prevent Mutant Huntingtin-Induced Neuronal Degeneration. Creus-Muncunill J, Rué L, Alcalá-Vida R, Badillos-Rodríguez R, Romaní-Aumedes J, Marco S, Alberch J, Perez-Otaño I, Malagelada C, Pérez-Navarro Mol Neurobiol. 2018 55(10): 7728-7742 https://doi.org/10.1007/s12035-018-0956-5