Genomic imprinting of the metabolic regulator gene Klf14 is regulated by a paternal sub-TAD anchored at Mest.

Maternally methylated Mest gDMR regulates Klf14 imprinting through allele-specific TAD structures in embryonic stem cells.

• Why it matters: Understanding how genomic imprinting is controlled at the Klf14 locus is crucial because variants in this gene are linked to type 2 diabetes and metabolic syndrome, with risk alleles only pathogenic when maternally inherited.
• What they did: The study used allele-specific 4C-seq, CRISPR-Cas9 deletions, and chromatin analysis in embryonic stem cells and pituitary cells to investigate the regulatory mechanisms, focusing on the Mest gDMR and TAD structures.
• The result: Findings show that the Mest gDMR influences Klf14 imprinting by modulating TAD structures in an allele-specific manner, with deletions leading to loss of Mest expression and biallelic Klf14 expression, revealing a long-range imprinting control mechanism.