Histone Lysine-to-Methionine Mutations Reduce Histone Methylation and Cause Developmental Pleiotropy1[OPEN]

• Published in: Plant physiology (Bethesda) Vol. 173; no. 4; pp. 2243 - 2252
• Main Authors: Sanders, Dean, Qian, Shuiming, Fieweger, Rachael, Lu, Li, Dowell, James A., Denu, John M., Zhong, Xuehua
• Format: Journal Article
• Language: English
• Published: American Society of Plant Biologists 15.02.2017
• DOI: 10.1104/pp.16.01499
• ISSN: 0032-0889

Transgenic plants expressing H3K36M mutations have a dominant-negative effect on the endogenous histone methylation landscape, leading to pleiotropic developmental defects. Epigenetic modifications play critical roles in diverse biological processes. Histone Lys-to-Met (K-to-M) mutations act as gain-of-function mutations to inhibit a wide range of histone methyltransferases and are thought to promote tumorigenesis. However, it is largely unknown whether K-to-M mutations impact organismal development. Using Arabidopsis ( Arabidopsis thaliana ) as a model system, we discovered that a transgene exogenously expressing histone 3 Lys-36 to Met mutation (K36M) acts in a dominant-negative manner to cause global reduction of H3K36 methylation. Remarkably, this dominant repressive activity is dosage-dependent and causes strong developmental perturbations including extreme branching and early flowering by affecting the expression of genes involved in developmental and metabolic processes. Besides the established pathological roles of K-to-M mutations in tumor cells, we demonstrate a physiological outcome for K-to-M induced H3K36 hypomethylation. This study provides evidence for a conserved dominant-negative inhibitory role of histone K-to-M mutation across the plant and animal kingdoms. We also highlight the unique ability of K36M mutations to alter plant developmental processes leading to severe pleiotropic phenotypes. Finally, our data suggests K-to-M mutations may provide a useful strategy for altering epigenetic landscapes in organisms where histone methyltransferases are uncharacterized.