Saturday, 23rd June 2018

Genome Dynamics and Function

      Functional organization of the mammalian genome



2016 07 26 GrupoMGomez 400px


María Gómez




Research summary:

One of the most fascinating challenges in genome biology is deciphering the non-coding genomic landscape, as the majority of the eukaryotic complexity is encoded in our regulatory elements. Studies in our lab focus on the functional relationship between the regions that regulate DNA replication initiation and transcription initiation, and how these nuclear processes take place within the context of a highly complex and compacted genomic chromatin environment.

During the last years, we studied how nucleosomes and chromatin structure influence the activation of DNA replication initiation sites using two complementary experimental systems: (i) mammalian genetic systems with altered DNA-nucleosome ratios, and (ii) the particular genomic arrangement of the early branched eukaryote Leishmania major. Collectively, we found that chromatin configurations strongly impact on the replication initiation landscape and that both the spatial and the temporal programme of DNA replication are linked to RNA polymerase kinetics. Building-up from that work, we are currently exploring in detail how replicating cells respond to altered chromatin scenarios and, in particular, how the crosstalk between transcription and replication is established to ensure genome stability. This integrative knowledge is of fundamental importance as there is mounting evidence showing that impairment in the coordination between both processes is a strong source of genomic instability, and that cellular aging and certain developmental disorders are associated with impaired chromatin structure and global genomic instability. To this aim we use a variety of genetic systems with altered chromatin structure, and address the replicative, transcriptional, and DNA damage responses to these chromatin scenarios with a combination of state-of-the-art approaches from single-molecule to genome-wide analysis.


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Latest publications:

  • Lombraña, R., Álvarez, A., Fernández-Justel, J. M., Almeida, R., Poza-Carrión, C., Gomes, F., Calzada, A., Requena, J. M. and Gómez, M. 2016. Transcriptionally driven DNA replication programme of the human parasite Leishmania major. Cell Rep, 16: 1-13.
  • Lombraña, R., Almeida, R., Revuelta, I., Madeira, S., Herranz, G., Saiz, N., Bastolla, U. and Gómez, M. 2013. High-resolution analysis of DNA synthesis start sites and nucleosome architecture at efficient mammalian replication origins. EMBO J. 32: 2631-2644.
  • Sequeira-Mendes, J., Diaz-Uriarte, R., Apedaile, A., Huntley, D., Brockdorff, N. and Gómez, M. 2009. Transcription initiation activity sets replication origin efficiency in mammalian cells. PLoS Genet. 5: e1000446.
  • Gómez, M. and Antequera, F. 2008. Overeplication of short DNA regions during S phase in human cells. GenesDev. 22: 375-38.