Characterization of DXZ4 conservation in primates implies important functional roles for CTCF binding, array expression and tandem repeat organization on the X chromosome.

Background: Comparative sequence analysis is a powerful means with which to identify functionally relevant non-coding DNA elements through conserved nucleotide sequence. The macrosatellite DXZ4 is a polymorphic, uninterrupted, tandem array of 3-kb repeat units located exclusively on the human X chromosome. While not obviously protein coding, its chromatin organization suggests differing roles for the array on the active and inactive X chromosomes.

Results: In order to identify important elements within DXZ4, we explored preservation of DNA sequence and chromatin conformation of the macrosatellite in primates. We found that DXZ4 DNA sequence conservation beyond New World monkeys is limited to the promoter and CTCF binding site, although DXZ4 remains a GC-rich tandem array. Investigation of chromatin organization in macaques revealed that DXZ4 in males and on the active X chromosome is packaged into heterochromatin, whereas on the inactive X, DXZ4 was euchromatic and bound by CTCF.

Conclusions: Collectively, these data suggest an important conserved role for DXZ4 on the X chromosome involving expression, CTCF binding and tandem organization.