Characterization of the ICCE Repeat in Mammals Reveals an Evolutionary Relationship with the DXZ4 Macrosatellite through Conserved CTCF Binding Motifs
| Autor: | Brian P. Chadwick, Natalia Westervelt |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CCCTC-Binding Factor X Chromosome Locus (genetics) Biology YY1 DNA sequencing X-inactivation Conserved sequence 03 medical and health sciences inactive X chromosome Tandem repeat X Chromosome Inactivation Genetics Animals Humans superloop anchor Thp5 Ecology Evolution Behavior and Systematics Conserved Sequence Phylogeny Mammals Binding Sites Base Sequence NBDY Intron DNA Methylation Chromatin 030104 developmental biology tandem repeat CTCF Evolutionary biology Genetic Loci Tandem Repeat Sequences Female Research Article |
| Zdroj: | Genome Biology and Evolution |
| ISSN: | 1759-6653 |
| Popis: | Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE. |
| Databáze: | OpenAIRE |
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