The lncRNA Locus Handsdown Regulates Cardiac Gene Programs and Is Essential for Early Mouse Development
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 e...
Saved in:
Published in | Developmental cell Vol. 50; no. 5; pp. 644 - 657.e8 |
---|---|
Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
09.09.2019
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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.
[Display omitted]
•The essential lncRNA Handsdown is haploinsufficient for embryonic development•The Handsdown RNA transcript is dispensable for cardiac gene regulation•The TAD association of Handsdown shifts during cardiac differentiation•Transcription of Handsdown regulates the cis-located Hand2 gene
Ritter et al. characterize an essential lncRNA locus, Handsdown, which regulates development by controlling cardiac gene programs during early vertebrate embryo formation. The Handsdown locus physically interacts with the Hand2 gene during cardiac differentiation and genetic ablation of Handsdown leads to elevated Hand2 levels. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1534-5807 1878-1551 |
DOI: | 10.1016/j.devcel.2019.07.013 |