DLK1DIO3

DLK1-DIO3, commonly referred to as the DLK1-DIO3 imprinted region, is a conserved imprinted gene cluster on human chromosome 14q32. It spans roughly 1.5 megabases and contains a mix of protein-coding, noncoding, and small RNA genes. The region is syntenic with a similar locus in mouse, located on chromosome 12 as Dlk1-Dio3.

The paternal allele of the region expresses the protein-coding gene DLK1 and RTL1, while the maternal allele expresses a large noncoding RNA gene MEG3 (also known as Gtl2 in mouse) together with an extensive cluster of small nucleolar RNA (snoRNA) genes. The DIO3 gene, encoding type 3 iodothyronine deiodinase, is also part of this regional locus. This arrangement results in reciprocal, parent-of-origin-specific expression across the region.

Expression is controlled by imprinting regulatory elements, including an imprinting control region and differentially methylated regions that establish distinct epigenetic marks on the paternal and maternal alleles. These epigenetic patterns govern the allele-specific transcription of the prototypic paternal protein-coding genes and the maternal noncoding RNAs.

Functionally, the DLK1-DIO3 region contributes to fetal and placental development and plays a role in growth and neurodevelopment. Disruptions of imprinting at this locus are associated with human imprinting disorders such as Kagami-Ogata syndrome (paternal imprinting defects or duplications of 14q32) and Temple syndrome (maternal uniparental disomy 14 or epimutations). Abnormal expression within this domain has also been observed in certain cancers and metabolic contexts, reflecting its broad influence on growth regulation and cellular differentiation.

Diagnosis and research often focus on DNA methylation testing of the region’s differential methylation marks to detect imprinting defects.