The human genome contains barely more protein-coding genes than that of a fruit fly. The more complex development and behaviour of mammals lies, not in the number of their genes, but in how those genes are controlled. The genome of mammals is full of switches that control when, where and how genes are switched on. These control switches - called enhancers - have previously been identified by a chemical flag that is added to the chromatin of enhancers when they are active (switched on). In chromatin, DNA is wrapped around a ball of proteins called histones to package up the genome. The previously known flag at enhancers is on the tail of histone molecules that protrude from chromatin and is thought to act as signal to other proteins. However Pradeepa and colleagues at the MRC Human Genetics Unit, together with a colleague at the Institut of Functional Epigenetics in Munich, have found a new chemical flag on histones that identifies a whole new set of enhancer elements in the genome. This chemical mark acts to physically disrupt the structure of chromatin. Not only does this work improve our understanding of how genes are controlled, but it is also important for understanding how the human genome impacts on health and disease. Most of the genetic variation in the human population that affects the risk of developing common diseases such as; cancer, stroke, diabetes, arthritis etc, is not in genes themselves, but in the enhancer elements that switch genes on.
Histone H3 globular domain acetylation identifies a new class of enhancers
Madapura M Pradeepa, Graeme R Grimes, Yatendra Kumar, Gabrielle Olley, Gillian C A Taylor, Robert Schneider and Wendy A Bickmore
Nature Genetics, 2016
Researchers at the MRC Human Genetics Unit have identified a biological barcode in mouse cells that could help explain how liver cancers develop in people.
The findings could lead to the development of new personalised treatments for the disease. The study, with Dr John Thomson as first author, sought to understand the chemical changes that take place in liver cells over time and how these changes can switch genes on or off, affecting the organ’s function.
The researchers focused on a key chemical found in liver cells – known as 5hmC – that can track and identify changes in the cell’s gene function, like a biological barcode. They showed for the first time how changes to this barcode can be monitored and used to predict whether a cell will become cancerous. This helps scientists to understand the chemical processes that can lead to the growth of liver cancers and may pave the way for treatments that are based on a patient’s personal genetic signature.
“This study provides an additional strategy to investigate the mechanisms of cancer progression and can pave the way to the identification of new cancer drug targets.”
Dr John Thomson, MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh
The study was funded by the Medical Research Council and Innovative Medicine Initiative and published in the journal Cancer Research.
Research paper published in Cancer Research