An epigenetic basis of inbreeding depression in maize

Inbreeding depression is widespread across plant and animal kingdoms and may arise from the exposure of deleterious alleles and/or loss of overdominant alleles resulting from increased homozygosity, but these genetic models cannot fully explain the phenomenon. Here we report epigenetic links to inbreeding depression in maize. Teosinte branched1/Cycloidea/Proliferating-cell-factor (TCP) transcription factors control plant growth and development. During successive inbreeding among highly inbred lines, thousands of genomic regions across TCP-binding sites (TBS) are hypermethylated through the H3K9me2-mediated pathway. These hypermethylated regions are accompanied by decreased chromatin accessibility, increased levels of the repressive histone marks H3K27me2 and H3K27me3, and reduced binding-affinity of maize TCP proteins to TBS. Consequently, hundreds of TCP-target genes involved in mitochondrion, chloroplast, and ribosome functions are downregulated, leading to reduced growth vigor. Conversely, random mating can reverse corresponding hypermethylation sites and TCP-target gene expression, restoring growth vigor. These results support a unique role of reversible epigenetic modifications in inbreeding depression.