Precisely controlled gene regulatory networks are
required during embryonic development to give
rise to various structures, including those of the cardiovascular system. Long non-coding RNA (lncRNA)
loci are known to be important regulators of these
genetic programs. We have identified a novel and
essential lncRNA locus Handsdown (Hdn), active in
early heart cells, and show by genetic inactivation
that it is essential for murine development. Hdn displays haploinsufficiency for cardiac development as
Hdn-heterozygous adult mice exhibit hyperplasia in
the right ventricular wall. Transcriptional activity of
the Hdn locus, independent of its RNA, suppresses
its neighboring gene Hand2. We reveal a switch in a
topologically associated domain in differentiation of
the cardiac lineage, allowing the Hdn locus to
directly interact with regulatory elements of the
Hand2 locus. |
