An epigenetic basis of inbreeding depression in maize

Inbreeding depression is linked to persistent epigenetic and gene expression changes, which are reversible by random mating. 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 development. During successive inbreeding among 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 down-regulated, 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.