MIR retrotransposons link the epigenome and the transcriptome of coding genes in acute myeloid leukemia.

ABSTRACT: DNMT3A and IDH1/2 mutations combinatorically regulate the transcriptome and the epigenome in acute myeloid leukemia; yet the mechanisms of this interplay are unknown. Using a systems approach within topologically associating domains, we find that genes with significant expression-methylation correlations are enriched in signaling and metabolic pathways. The common denominator across these methylation-regulated genes is the density in MIR retrotransposons of their introns. Moreover, a discrete number of CpGs overlapping enhancers are responsible for regulating most of these genes. Established mouse models recapitulate the dependency of MIR-rich genes on the balanced expression of epigenetic modifiers, while projection of leukemic profiles onto normal hematopoiesis ones further consolidates

SUBMITTER: Telonis AG 

PROVIDER: S-EPMC9622910 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature