LONG-RANGE CIS EFFECTS OF ECTOPIC X-INACTIVATION CENTERS ON A MOUSE AUTOSOME

In mammals, the X chromosome is unique in being capable of complete in activation. Such X inactivation evolved to compensate for gene dosage differences between females with two X chromosomes and males with one( 1). Transcriptional silencing of a, single female X chromosome is cont rolled in cis by Xist(2), whose RNA product coats the inactive X chrom osome (X(i))(3), and the X-inactivation centre (Xic)(4). A transgenic study limited the Xic to 450 kilobases including Xist, and demonstrate d that it is sufficient to initiate X inactivation(5). Here we report that ectopic Xist RNA completely coats transgenic chromosome 12. Expre ssion of genes over 50 centimorgans was reduced two-fold and was detec ted only from the normal homologue in fibroblasts. Moreover, ectopic X ic action resulted in chromosome-wide changes that are characteristic of the X(i): DNA replication was delayed, and histone H4 was markedly hypoacetylated. Our findings suggest long-range cis effects on the aut osome similar to those of X inactivation, and imply that the Xic can b oth initiate X inactivation and drive heterochromatin formation, Thus, the potential for chromosome-wide gene regulation is not intrinsic to X-chromosome DNA, but can also occur on autosomes possessing the Xic.