This article may be too technical for most readers to understand. (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.[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]
References
edit- ^ Ong CT, Corces VG (April 2014). "CTCF: an architectural protein bridging genome topology and function". Nature Reviews. Genetics. 15 (4): 234–46. doi:10.1038/nrg3663. PMC 4610363. PMID 24614316.
- ^ a b c Giacalone J, Friedes J, Francke U (May 1992). "A novel GC-rich human macrosatellite VNTR in Xq24 is differentially methylated on active and inactive X chromosomes". Nature Genetics. 1 (2): 137–43. doi:10.1038/ng0592-137. PMID 1302007. S2CID 20003755.
- ^ Chadwick BP (August 2008). "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". Genome Research. 18 (8): 1259–69. doi:10.1101/gr.075713.107. PMC 2493436. PMID 18456864.
- ^ Pohlers M, Calabrese JM, Magnuson T (August 2014). "Small RNA expression from the human macrosatellite DXZ4". G3: Genes, Genomes, Genetics. 4 (10): 1981–9. doi:10.1534/g3.114.012260. PMC 4199704. PMID 25147189.
- ^ Deng X, Ma W, Ramani V, Hill A, Yang F, Ay F, Berletch JB, Blau CA, Shendure J, Duan Z, Noble WS, Disteche CM (August 2015). "Bipartite structure of the inactive mouse X chromosome". Genome Biology. 16 (1): 152. doi:10.1186/s13059-015-0728-8. PMC 4539712. PMID 26248554.
- ^ Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, Aiden EL (December 2014). "A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping". Cell. 159 (7): 1665–80. doi:10.1016/j.cell.2014.11.021. PMC 5635824. PMID 25497547.
- ^ Darrow EM, Huntley MH, Dudchenko O, Stamenova EK, Durand NC, Sun Z, et al. (August 2016). "Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture". Proceedings of the National Academy of Sciences of the United States of America. 113 (31): E4504-12. Bibcode:2016PNAS..113E4504D. doi:10.1073/pnas.1609643113. PMC 4978254. PMID 27432957.