DXZ4

{{technical|date=April 2019}}

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.{{cite journal | vauthors = Ong CT, Corces VG | title = CTCF: an architectural protein bridging genome topology and function | journal = Nature Reviews. Genetics | volume = 15 | issue = 4 | pages = 234–46 | date = April 2014 | pmid = 24614316 | pmc = 4610363 | doi = 10.1038/nrg3663 }}

In addition to being enriched in CpG-islands,{{cite journal | vauthors = Giacalone J, Friedes J, Francke U | title = A novel GC-rich human macrosatellite VNTR in Xq24 is differentially methylated on active and inactive X chromosomes | journal = Nature Genetics | volume = 1 | issue = 2 | pages = 137–43 | date = May 1992 | pmid = 1302007 | doi = 10.1038/ng0592-137 | s2cid = 20003755 }} DXZ4 transcribes long non-coding RNAs (lncRNAs) and small RNAs of unknown function.{{cite journal | vauthors = Chadwick BP | title = DXZ4 chromatin adopts an opposing conformation to that of the surrounding chromosome and acquires a novel inactive X-specific role involving CTCF and antisense transcripts | journal = Genome Research | volume = 18 | issue = 8 | pages = 1259–69 | date = August 2008 | pmid = 18456864 | pmc = 2493436 | doi = 10.1101/gr.075713.107 }}{{cite journal | vauthors = Pohlers M, Calabrese JM, Magnuson T | title = Small RNA expression from the human macrosatellite DXZ4 | journal = G3: Genes, Genomes, Genetics | volume = 4 | issue = 10 | pages = 1981–9 | date = August 2014 | pmid = 25147189 | pmc = 4199704 | doi = 10.1534/g3.114.012260 }} 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. 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. 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”.{{cite journal | vauthors = Deng X, Ma W, Ramani V, Hill A, Yang F, Ay F, Berletch JB, Blau CA, Shendure J, Duan Z, Noble WS, Disteche CM | title = Bipartite structure of the inactive mouse X chromosome | journal = Genome Biology | volume = 16 | pages = 152 | date = August 2015 | issue = 1 | pmid = 26248554 | pmc = 4539712 | doi = 10.1186/s13059-015-0728-8 | doi-access = free }}

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.{{cite journal | vauthors = Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, Aiden EL | title = A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping | journal = Cell | volume = 159 | issue = 7 | pages = 1665–80 | date = December 2014 | pmid = 25497547 | pmc = 5635824 | doi = 10.1016/j.cell.2014.11.021 }} Knockout of the DXZ4 locus revealed loss of this structural conformation on the Xi with chromosome wide silencing being maintained.{{cite journal | vauthors = Darrow EM, Huntley MH, Dudchenko O, Stamenova EK, Durand NC, Sun Z, Huang SC, Sanborn AL, Machol I, Shamim M, Seberg AP, Lander ES, Chadwick BP, Aiden EL | display-authors = 6 | title = Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 31 | pages = E4504-12 | date = August 2016 | pmid = 27432957 | pmc = 4978254 | doi = 10.1073/pnas.1609643113 | bibcode = 2016PNAS..113E4504D | doi-access = free }}