Chromatin and Mitochondrial Disease

CHROMATIN AND MITOCHONDRIAL DISEASE

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There is a constant interaction between mitochondria and the nucleus, with changes in each compartment affecting homeostasis in the other. DNA replication, histone modification and transcription all have specific metabolic requirements and depend on metabolites such as ATP and other nucleotides for DNA and RNA synthesis or NAD+ for Sirtuin-dependent deacetylation. The metabolic demands of the nuclear genome therefore provide a direct link between gene expression on the one hand and metabolic status of the cell, tissue or organism on the other.

We mainly use innovative DamID-based technology to study cell-type specific regulation of gene expression in the context of in vivo mitochondrial dysfunction.

RELEVANT PUBLICATIONS

van den Ameele J, Krautz R & Brand AH (2019)
TaDa! Analysing cell type-specific chromatin in vivo with Targeted DamID.
Curr Opin Neurobiol 56, 160-166

Aloia L, McKie MAlexander, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Cigliano RAiese, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA & Huch M (2019)
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Nat Cell Biol 21, 1321-1333.

Cheetham SW, Gruhn WH, van den Ameele J, Krautz R, Southall TD, Kobayashi T, M Surani A & Brand AH (2018)
Targeted DamID reveals differential binding of mammalian pluripotency factors.
Development 145, dev170209