Biology: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]
References
- ↑ "CTCF: an architectural protein bridging genome topology and function". Nature Reviews. Genetics 15 (4): 234–46. April 2014. doi:10.1038/nrg3663. PMID 24614316.
- ↑ 2.0 2.1 2.2 "A novel GC-rich human macrosatellite VNTR in Xq24 is differentially methylated on active and inactive X chromosomes". Nature Genetics 1 (2): 137–43. May 1992. doi:10.1038/ng0592-137. PMID 1302007.
- ↑ "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. August 2008. doi:10.1101/gr.075713.107. PMID 18456864.
- ↑ "Small RNA expression from the human macrosatellite DXZ4". G3: Genes, Genomes, Genetics 4 (10): 1981–9. August 2014. doi:10.1534/g3.114.012260. PMID 25147189.
- ↑ "Bipartite structure of the inactive mouse X chromosome". Genome Biology 16 (1): 152. August 2015. doi:10.1186/s13059-015-0728-8. PMID 26248554.
- ↑ "A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping". Cell 159 (7): 1665–80. December 2014. doi:10.1016/j.cell.2014.11.021. PMID 25497547.
- ↑ "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. August 2016. doi:10.1073/pnas.1609643113. PMID 27432957. Bibcode: 2016PNAS..113E4504D.
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