DXZ4

DXZ4 is a variable number tandemly repeated DNA sequence. In humans it is composed of 3kb monomers containing a highly conserved CTCF binding site. CTCF is a transcription factor protein and the main insulator responsible for partitioning of chromatin domains in the vertebrate genome.^[1]

In addition to being enriched in CpG-islands,^[2] DXZ4 transcribes long non-coding RNAs (lncRNAs) and small RNAs of unknown function.^[3][4] Repeat copy number of DXZ4 is highly polymorphic in human populations (varying between 50 and 100 copies). DXZ4 is one of many large tandem repeat loci defined as macrosatellites.^[2] Several macrosatellites have been described in humans and share similar features, such as high GC content, large repeat monomers, and high variability for repeat copy number within populations.^[2] DXZ4 plays an important role in the unique structural conformation of the inactive X chromosome (Xi) in female somatic cells by acting as a hinge point between two large “super domains”.^[5]

In addition to acting as the primary division between domains, DXZ4 forms long-range interactions with a number of other repeat rich regions along the inactive X chromosome.^[6] Knockout of the DXZ4 locus revealed loss of this structural conformation on the Xi with chromosome wide silencing being maintained.^[7]