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Abstract
Recent investigations have implicated long antisense noncoding RNAs in the epigenetic
regulation of chromosomal domains. Here we show that Kcnq1ot1 is an RNA polymerase
II-encoded, 91 kb-long, moderately stable nuclear transcript and that its stability
is important for bidirectional silencing of genes in the Kcnq1 domain. Kcnq1ot1 interacts
with chromatin and with the H3K9- and H3K27-specific histone methyltransferases G9a
and the PRC2 complex in a lineage-specific manner. This interaction correlates with
the presence of extended regions of chromatin enriched with H3K9me3 and H3K27me3 in
the Kcnq1 domain in placenta, whereas fetal liver lacks both chromatin interactions
and heterochromatin structures. In addition, the Kcnq1 domain is more often found
in contact with the nucleolar compartment in placenta than in liver. Taken together,
our data describe a mechanism whereby Kcnq1ot1 establishes lineage-specific transcriptional
silencing patterns through recruitment of chromatin remodeling complexes and maintenance
of these patterns through subsequent cell divisions occurs via targeting the associated
regions to the perinucleolar compartment.