Epigenetics and How it Relates to Kabuki Syndrome
Epigenetics literally means ‘above genetics’. The epigenome doesn’t change your DNAi but it decides how much or whether particular genes are expressed in different cells in your body. In other words, your DNA must be told whether to express the genes within it. This is done by proteins (genes) within the epigenome. KMT2D (MLL2) and KDM6A are two of those epigenetic genes. And since they are malfunctioning, they are failing to tell certain genes within the DNA to ‘get to work’.
It is presently known that KMT2D gene mutation is responsible for approximately 75% of individuals with Kabuki Syndrome. More recently, mutations of the KDM6A gene have been discovered in 9% of individuals who tested negative for KMT2D gene mutation. Interestingly, the functions of KDM6A and KMT2D are related to each other. They function by either adding (in the case of KMT2D) an activating methyl group or removing (in the case of KDM6A) repressive methyl groupsi to specific amino acids in a protein called Histonei H3. The H3 protein can either be modified by repressive (H3K27me3) or active (H3K4me3) methyl groups. Since the KMT2D and KDM6A genes have mutations, the KMT2D is not adding the active methyl groups or KDM6A is not removing the repressive groups. In essence, although they are doing the opposite activity, the result is the same – repressing (closed chromatini) the open chromatin state of the H3 protein. As a result, the cells in the body that require gene activation through H3 protein, must now do without.
Sure you are! Below you will find a refreshingly comical explanation from Hank Green! And then check out What is Epigentics for further easy-to-understand lessons!