Dr Stephen Rea

Lecturer in Biochemistry
Principal Investigator

Research interests

  • Chromatin regulation of the DNA damage response
  • Histone modifications in normal development and disease
  • Epigenetic regulation of gene expression

Research overview

Eukaryotic DNA is wrapped around histone proteins to form chromatin. This serves to package the DNA into the nucleus, but also facilitates the regulation of DNA-templated processes such as replication, transcription and repair. This regulation can be achieved through modifying the histone proteins by the addition of chemical groups or small peptides. Such modifications can either change how tightly the DNA is wrapped- making it more accessible, or they can recruit other factors that act on the DNA.

These modifications also play a role in epigenetics; acting above the level of DNA to maintain gene expression patterns from cell to cell, and hence dictating the proper development of an organism. Considering the fundamental involvement of histone modifications in all these processes, it is not surprising that defects in these modifications can cause diseases.

To better understand how these chromatin modifications help to regulate such important processes, we are studying the human MOF complex in cultured human cells and tumor cell lines. This complex contains at least two histone modifying enzymes: hMOF and hMSL2. hMOF is the enzyme responsible for the acetylation of histone H4 at lysine 16 (fig 1), and hMSL2 is able to add ubiquitin peptides to histone H2B at lysine 34.

Recently, it was found that loss of hMOF and also reduction in H4K16 acetylation levels are frequent occurrences in various human cancers (fig 2). Thus, studying hMOF and hMSL2 allows us to investigate the role of these enzymes and their histone modifications in normal development and their involvement in cancer.

To read more about our projects or meet our group members, see our group pages.

Selected publications

  • Whitton L, Apostolova G, Rieder D, Dechant G, Rea S, Donohoe G, Morris DW. Genes regulated by SATB2 during neurodevelopment contribute to schizophrenia and educational attainment. PLoS Genet 14(7): e1007515. https://doi.org/10.1371/journal.pgen.1007515 (2018)
  • Lai Z, Moravcova S, Canitrot Y, Andrzejewski LP, Walshe DM, Rea S, Msl2 is a novel component of the vertebrate DNA damage response. PLoS ONE 8(7): e68549. doi:10.1371/journal.pone.0068549 (2013)
  • Chubb JE, Rea S, Core and linker histone modifications involved in the DNA damage response. Subcell Biochem 50: 17-42 (2010)
  • Pfister S, Rea S, Taipale M, Mendrzyk F, Straub B, Ittrich C, Thuerigen O, Sinn HP, Akhtar A, Lichter P. The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma. Int J Cancer 122: 1207-1213 (2008)
  • Taipale M, Rea S, Richter K, Vilar A, Lichter P, Imhof A, Akhtar A. hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells. Mol Cell Biol 25: 6798-6810 (2005)