DXZ4 — Mediated Wiki

'''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.<ref name="pmid24614316">{{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 }}</ref>

In addition to being enriched in CpG-islands,<ref name="Giacalone_1992">{{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 }}</ref> ''DXZ4'' transcribes long non-coding RNAs (lncRNAs) and small RNAs of unknown function.<ref name="pmid18456864">{{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 }}</ref><ref name="pmid25147189">{{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 }}</ref> 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.<ref name="Giacalone_1992" /> 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.<ref name="Giacalone_1992" /> ''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”.<ref name="pmid26248554">{{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 | article-number = 152 | date = August 2015 | issue = 1 | pmid = 26248554 | pmc = 4539712 | doi = 10.1186/s13059-015-0728-8 | doi-access = free }}</ref>

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.<ref name="pmid25497547">{{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 }}</ref> Knockout of the ''DXZ4'' locus revealed loss of this structural conformation on the Xi with chromosome wide silencing being maintained.<ref>{{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 }}</ref>

== References == {{reflist}}

Category:Gene expression Category:Repetitive DNA sequences Category:Transcription factors