It occurs early in female development and shuts down gene expression from the X chromosome (Xi) chosen to become inactive by repackaging the DNA into facultative heterochromatin. XCI is the mammalian form of dosage compensation, an epigenetic process that serves to balance the levels of X-linked gene expression in the two sexes. Because of its physical location on the X chromosome, DXZ4 is exposed to the process of X-chromosome inactivation (XCI). Most occupy specific locations on one or two chromosomes, like the X-linked macrosatellite DXZ4, which is unique to Xq23. Macrosatellites are tandem repeat DNA with some of the largest individual repeat units (most >2 kb), which can extend over hundreds to thousands of kilobases.

ĭespite a lack of functional understanding for these sequences, their contribution to disease susceptibility is obvious, as is demonstrated by the devastating impact of simple repeat expansions or macrosatellite contraction. For some tandem repeat DNA, deciphering of function is assisted by location, such as the alpha satellite DNA that defines active centromeres to the telomeric minisatellite, but the roles of others in our genome remain unknown, resulting in opinions in the past that they serve no purpose. The size of the individual repeat unit varies substantially, from the simple microsatellite composed of individual repeat units of 1 to 6 bp spanning tens to hundreds of base pairs to those consisting of individual repeat units of several kilobases that can cover hundreds to thousands of kilobases. The tandem repeats consist of homologous DNA sequences arranged head to tail, and the number of repeat units is invariably polymorphic from one individual to the next.

Over two-thirds of the human genome is likely to be composed of repetitive DNA, of which a significant proportion is tandem repeat DNA. ConclusionsĬharacterization of Dxz4 reveals substantial differences in the organization of DNA sequence, chromatin packaging, and the mode of transcription, so the potential roles performed by this sequence in mouse have probably diverged from those on the primate X chromosome. Ctcf binds Dxz4 but is not exclusive to the inactive X chromosome, as evidenced by association in some males and equal binding to both X chromosomes in trophoblast stem cells. However, many features that characterize primate DXZ4 differ in mouse, including the overall size of the array, the mode of transcription, the chromatin organization and conservation between adjacent repeat units of DNA sequence and length. Furthermore, we provide evidence of DXZ4 in a conserved location downstream of the PLS3 gene in a diverse group of mammals, and reveal that DNA sequence conservation is restricted to the CTCF binding motif, supporting a central role for this protein at this locus.

Here we extend our comparative genome analysis and report the identification and characterization of the mouse homolog of the macrosatellite. Because its DNA sequence diverges rapidly beyond the New World monkeys, the existence of DXZ4 outside the primate lineage is unknown. It is packaged into heterochromatin on the active X chromosome but into euchromatin and bound by the epigenetic organizer protein CTCF on the inactive X chromosome. The X-linked macrosatellite DXZ4 is a large homogenous tandem repeat that in females adopts an alternative chromatin organization on the primate X chromosome in response to X-chromosome inactivation.

Sequencher reverse complement