The mouse DXZ4 homolog retains Ctcf binding and proximity to Pls3 despite substantial organizational differences compared to the primate macrosatellite.
BACKGROUND
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. 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. Because its DNA sequence diverges rapidly beyond the New World monkeys, the existence of DXZ4 outside the primate lineage is unknown.


RESULTS
Here we extend our comparative genome analysis and report the identification and characterization of the mouse homolog of the macrosatellite. 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. 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. 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.


CONCLUSIONS
Characterization 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.
Andrea H
AH
Horakova
J Mauro
JM
Calabrese
Christine R
CR
McLaughlin
Deanna C
DC
Tremblay
Terry
T
Magnuson
Brian P
BP
Chadwick
D000818:Animals; D041702:BALB 3T3 Cells; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002843:Chromatin / Q000235:genetics; D003001:Cloning, Molecular; D055028:Comparative Genomic Hybridization; D017124:Conserved Sequence; D019175:DNA Methylation; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences; D014960:X Chromosome / Q000235:genetics
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004276:DNA, Satellite; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D012097:Repressor Proteins; C026742:plastin