Lisa L. Hall 1, Meg Byron 1, Kosuke Sakai 2, Laura Carrel 2, Huntington F. Willard 2, and Jeanne B. Lawrence 1, @,
1 Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655; and 2 Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106
@ To whom reprint requests should be addressed. E-mail: jeanne.lawrence@umassmed.edu
It has been believed that XIST RNA requires a discrete window in
early development to initiate the series of
chromatin-remodeling events that form the heterochromatic inactive
X chromosome. Here we investigate four adult male HT-1080 fibrosarcoma
cell lines expressing ectopic human XIST and demonstrate that these post-differentiation
cells can undergo chromosomal inactivation outside of any normal developmental
context. All four clonal lines inactivated the transgene-containing autosome
to varying degrees and with variable stability. One clone in particular
consistently localized the ectopic XIST RNA to a discrete chromosome territory
that exhibited striking hallmarks of inactivation, including long-range
transcriptional inactivation. Results suggest that some post-differentiation
cell lines are capable of de novo chromosomal inactivation;
however, long-term retention of autosomal inactivation was less common,
which suggests that autosomal inactivation may confer a selective disadvantage.
These results have fundamental significance for understanding genomic programming
in early development.
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