IMIM - Institut Hospital del Mar d'Investigacions Mèdiques

Chromatin dynamics in cancer cells Sandra Peiró

One of the most important lessons we have learned the last years, is that the determination of the sequence is only the first step to understand genome function. Mutations are an extreme case of gene modulation; most common changes in the genome function consist in fluctuations in gene expression, temporary silencing or temporary activation. Several mechanisms modulate genome function: At a transcriptional level, the availability of the transcription factor machinery at specific sites. Epigenetic modifications are also capable to modify the genetically encode information, for example via histone modifications or DNA methylation. Finally, changes in higher-order chromatin organization and gene positioning within the nucleus alter functional properties of genome regions.

The existence of mechanisms that modulate the output of genomes makes it clear that a true understanding of genome function requires integration of what we have learned about genome sequence with what we are still discovering about how genomes are modified and importantly how they are organized in vivo in the nucleus.

What it is happening in terms of chromatin dynamics and 3D chromatin architecture in cancer cells or better, in the acquisition of malignant traits (Cancer and EMT) it is poorly understood.

Our main research objective is focused on the characterization of chromatin dynamics in cancer and in EMT. Specifically, our main aims are the following:

  • Epigenetic modifications: Based in our previous publications we will focus out attention to oxidized Histone H3 (oxH3).
    • OxH3 in DNA Damage Response (DDR): Our previous data suggest that oxH3 and LOXL2 proteins could have a role in DDR. A missregulation of this pathway could be implicated in the acquisition of resistance to anti-cancer drugs.
    • Genome-wide localization of oxH3.
    • OxH3 readers identification: the existence of a oxH3 would suggest that there are proteins with specificity for this state. Recognition of oxH3 could occur through proteins known to recognize unmethylated histone tails, which suggest that entire new classes of histone “readers” with specificity for oxidized H3 might remain to be identified.
    • LOXL family members as a new family of histone-modifying enzymes.
    • Identification of new substrates for LOXL2
  • 3D Chromatin structure: we are planning to map the 3D chromatin state during the EMT process and in cancer cells using the Hi-C method. A method that is capable of identifying long-range interactions in an unbiased, genome-wide fashion. We will combine Hi-C with other genome-wide techniques, such us ChIP-seq and RNA seq.
    • To map the chromatin state during EMT.
    • To map the chromatin state in cancer cells. We postulate that the spatial chromosome architecture will be linked with the acquisition of somatic copy-number alterations (SCNA) in cancer cells.
  • Drug repurposing: The main objective of this project is to find potential drugs capable of inhibiting the epigenetic activity of LOXL2 through a drug-repurposing project. Drug repurposing consists in find new therapeutic uses for existing drugs on the market.

Latest publications

1. Herranz N, Dave N, Millanes-Romero A, Morey L, Díaz V, Lórenz-Fonfría V, Gutierrez-Gallego R, Jerónimo C, Di Croce L, García de Herreros A and Peiró S. LOXL2 is a Histone H3 K4 deaminase. Molecular Cell (2012). Corresponding author. Cover and a Preview. More

2. Millanes-Romero A, Herranz N, Loubat J, Iturbide A, Perrera V, Gil J, Jenuwein T, García de Herreros A and Peiró S. Regulation of Heterochromatin Transcription by Snail1/ LOXL2 During Epithelial to Mesenchymal Transition. Molecular Cell (2013). More

Contact

Coordinator:
Sandra Peiró

Tel:
933160434

Fax:
933160410

Dr. Aiguader, 88, 1er pis
08003 Barcelona

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