▷ Epigenetics and Metabolism Research Group

Lab presentation

Modifications of the chromatin fibre, such as the methylation of DNA or the acetylation of histones, are commonly referred to as epigenetic marks. These marks are understood as a way of storing information – of ‘bookmarking’ the genome so the cell remembers which genes to read. However, these processes are intimately tied to metabolism, as they both consume and produce metabolites which tie in to the wider metabolic network of the cell. Despite studies about how metabolism affects this ‘bookmarking’, to what extent the massive scale of these processes affects metabolism in turn is little understood or appreciated.

We aim to investigate these other functions and impacts of epigenetic processes, especially histone methylation. Taking advantage of the abundance of massive biological datasets available, we employ an interdisciplinary approach, combining computational analyses for discovery and hypothesis formation with experimental validation in different experimental systems.

Projects

Does histone methylation play a role as a metabolic process?

From analyses of massive datasets of gene expression in human healthy and cancerous samples, we have discovered that the expression of genes encoding histone methyltransferases is strongly associated with the expression of key metabolic genes with a similar biochemical function. This is evidence for a metabolic role of histone methylation that seems to have little measurable impact on gene expression. Intriguingly, the metabolic pathways that associate with histone methylation are changed markedly in cancerous samples.

We aim to:

investigate this metabolic role experimentally in living cells and organisms;
understand how the metabolic role of histone methylation contributes to cancer aggressiveness; and
understand how the expression of histone methyltransferase genes is co-ordinated among themselves and with metabolism.

Lab people

Marcos Francisco Pérez Browne

PhD - Ramon y Cajal

Biography

Originally from the British island of Jersey, Marcos first came to Barcelona in 2013 to undertake doctoral research at the Centre for Genomic Regulation (CRG) under the supervision of Prof. Ben Lehner, focussing on inter-individual physiological variation and intergenerational inheritance in the popular model organism C. elegans.

From 2020 to 2022 Marcos did postdoctoral training under the supervision of Dr. Peter Sarkies, first at the London Institute for Medical Sciences (LMS MRC) and later the University of Oxford, working on co-ordination of mitochondrial and nuclear gene expression and on the role of epigenetics in metabolism. During this time Marcos learned techniques in computational biology and analysis of large datasets in order to complement his earlier experimental research.

In 2023 Marcos started his group at the Barcelona Institute of Molecular Biology (CSIC IBMB) as a Ramon y Cajal researcher, combining computational and experimental approaches to molecular biology.

Mikel Freire

Master's Student

Selected publications

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Perez, M.F. and Sarkies, P., 2023. Histone methyltransferase activity affects metabolism in human cells independently of transcriptional regulation. PLoS Biology, 21(10), p.e3002354. doi: 10.1371/journal.pbio.3002354

Wilson, R., Le Bourgeouis, M., Perez, M.F. & Sarkies. P*. 2023. Fluctuations in chromatin state at regulatory loci occur spontaneously under relaxed selection and are associated with epigenetically inherited variation in C. elegans gene expression. PLoS Genetics, in press. doi: 10.1101/2022.09.29.510125

Perez, M.F*. & Sarkies. P*. 2021. Malignancy and NF-κB signalling strengthen coordination between expression of mitochondrial and nuclear-encoded oxidative phosphorylation genes. Genome Biology, 22(1), p1-24. doi: 10.1186/s13059-021-02541-6. *co-corresponding author

Perez, M.F., Shamalnasab, M., Mata-Cabana, A., Olmedo M., Francesconi, M. & Lehner, B. 2021. Neuronal perception of the social environment generates an inherited memory that controls the development and generation time of C. elegans. Current Biology, 31(19), p4256-4268. doi: 10.1016/j.cub.2021.07.031

Perez, M.F. & Lehner, B. 2019. Intergenerational and transgenerational epigenetic inheritance in animals. Nature Cell Biology, 21(2), p143-151. doi: 10.1038/s41556-018-0242-9

Perez, M. F., & Lehner, B. 2019. Vitellogenins-yolk gene function and regulation in Caenorhabditis elegans. Frontiers in Physiology, 10, p1067. doi: 10.3389/fphys.2019.01067

Perez, M. F., & Lehner, B. 2019. Per què ens interessa la herència no genètica?. In Deu aportacions catalanes a la ciència actual. Editorial: Galaxia Gutenberg, ISBN: 9788417747909

Offenburger, S.L., Perez, M.F. & Lehner B. 2018. Memory of ancestral mitochondrial stress. Nature Cell Biology. 21(3), p303-304. doi: 10.1038/s41556-018-0255-4

Perez, M.F.⁺, Francesconi, M.⁺, Hidalgo-Carcedo, C. & Lehner, B., 2017. Maternal age generates phenotypic variation in Caenorhabditis elegans. Nature, 552(7683), p106-109. doi: 10.1038/nature25012 ⁺joint first author

Schumacher, J., Waite, C.J., Bennett, M.H., Perez, M.F., Shethi, K. & Buck, M., 2014. Differential secretome analysis of Pseudomonas syringae pv tomato using gel-free MS proteomics. Frontiers in Plant Science, 5, p242. doi: 10.3389/fpls.2014.00242

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