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The Department of Biochemistry at the University of Oxford is a centre for world class research and teaching of all aspects of Biochemistry by staff from many different backgrounds and nationalities. Our research addresses a wide range of questions relating to the fundamental basis of all cellular life from man to microbes. This work explains the structures and functions of proteins and nucleic acids, and in doing so addresses the mechanisms of many human diseases. Using this knowledge, other researchers aim to create new vaccines, antiviral and antibacterial therapies to protect and treat humans across the world.
You can read more about the details of our current work and other aspects of the department, including undergraduate teaching and public outreach activities, on these web pages.
Professor Mark Sansom, Head of Department
News Highlight
Two arms secure gene transcription at the right sites
New findings that shed light on how epigenetic components in mammals shape transcription have been published by the Klose group.
The Cell Reports paper, a collaborative effort between labs in Oxford, Japan and the USA, reveals how a key histone-modifying enzyme is targeted to promoters and helps ensure appropriate gene expression (1). The findings provide an important step towards understanding how an epigenetic change can influence transcription.
Figure 1. Schematic showing that the chromatin-modifying complex SET1 is targeted to active genes at CpG islands via its component CFP1
(Click to Enlarge)
From bacteria through to yeast and mammals, huge efforts have been made to understand how DNA-encoded information is used. In higher organisms, this includes elucidating how epigenetic factors control the way in which genes are switched on and off. 'We understand a lot about transcription factors that recognise specific DNA sequences,' says Professor Klose, 'but how do we bring in the epigenetic component? Does epigenetic information influence how our DNA sequences are used, thereby supporting complex human processes and ultimately differentiating us from more simple species?'
One important epigenetic feature is chromatin modification, which includes H3K4me - methylation of histone H3 on lysine 4 - a mark that is generally associated with regulatory regions of DNA. 'We know that most actively transcribed genes sit in an epigenetic state that is permissive for gene transcription and that this is associated with H3K4me,' explains Professor Klose. 'Active genes have histones with this methylation, whereas inactive ones don't. But we don't know why or how this happens.'
Work in the Klose lab focuses on understanding epigenetics in the context of CpG islands (CGIs). These are regulatory elements made up of non-methylated CpG dinucleotides. CGIs are associated with promoters and are epigenetically modified, including acquiring H3K4me. However, not all CGIs have high levels of H3K4me, raising the question of how the methylation complex is recruited to the appropriate subset of CGIs so that H3K4me can be placed on them.
