Investigating imprinting at the Kcnk9 locus

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED


We inherit genes from our fathers and mothers and for most of our genes the copies we receive from either parent are equally active. An important exception to this general rule occurs in a process called genomic imprinting, whereby one gene copy is deliberately silenced. These imprinted genes are important in determining how the fetus grows and how infants adapt their physiology to life outside the womb. Imprinted genes behave in this manner because they are marked in different ways in the male and female germ cells (sperm and eggs). How these genes are so marked is not fully known, and it is important to find out, because if the marking process goes wrong problems in fertility or developmental abnormalities may arise. The marking involves a modification of the gene by DNA methylation, which can be faithfully passed on from the germ cells to all of the cells of the offspring. In this study, we are investigating how the specific organisation of these genes in the chromosome signals to the molecular machinery to add DNA methylation at the correct sites.


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Description Genomic imprinting is an important epigenetic mechanism in mammals that results in monoallelic silencing of a subset of our genes in a strict parent-of-origin manner. Despite the recognised importance of imprinted genes in growth and development of the mammalian embryo, we still do not fully understand how many genes in our genome are imprinted and how monoallelic expression of these genes is regulated.

We identified Kcnk9, a gene encoding a potassium channel of the TASK domain family, as a candidate imprinted gene by purely sequence-based predictions. In this project, we confirmed that Kcnk9 expression was imprinted with maternal-allele-specific expression. To investigate the basis for imprinted expression, we screened the chromosome environment of Kcnk9. Although we found that Kcnk9 does not have its own gamete-derived DNA methylation imprint mark, a candidate imprinting control region for Kcnk9 with this property was identified at a neighbouring locus Peg13. Work from other groups has shown that mutations in Kcnk9 causes a distinct form of mental retardation, so it is conceivable that errors in epigenetic marking the Peg13 control region could have a similar effect.
Sectors Healthcare