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PMID: 23369715 Published · ppublish English Journal Article

The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse.

Developmental cell ·Vol. 24 ·No. 2 ·2013-01-28 ·Pages 206-14

Grote P, Wittler L, Hendrix D, Koch F, Währisch S, Beisaw A, Macura K, Bläss G, Kellis M, Werber M, Herrmann BG

Abstract

The histone-modifying complexes PRC2 and TrxG/MLL play pivotal roles in determining the activation state of genes controlling pluripotency, lineage commitment, and cell differentiation. Long noncoding RNAs (lncRNAs) can bind to either complex, and some have been shown to act as modulators of PRC2 or TrxG/MLL activity. Here we show that the lateral mesoderm-specific lncRNA Fendrr is essential for proper heart and body wall development in the mouse. Embryos lacking Fendrr displayed upregulation of several transcription factors controlling lateral plate or cardiac mesoderm differentiation, accompanied by a drastic reduction in PRC2 occupancy along with decreased H3K27 trimethylation and/or an increase in H3K4 trimethylation at their promoters. Fendrr binds to both the PRC2 and TrxG/MLL complexes, suggesting that it acts as modulator of chromatin signatures that define gene activity. Thus, we identified an lncRNA that plays an essential role in the regulatory networks controlling the fate of lateral mesoderm derivatives.

MeSH Terms
Animals Cell Differentiation/genetics DNA Methylation Embryo, Mammalian/embryology,metabolism Embryonic Development Forkhead Transcription Factors/metabolism Heart/embryology Histone-Lysine N-Methyltransferase Histones/metabolism Homeodomain Proteins/metabolism Mice Molecular Sequence Data Myeloid-Lymphoid Leukemia Protein/metabolism Polycomb Repressive Complex 2/metabolism Promoter Regions, Genetic RNA, Long Noncoding/genetics,metabolism Transcription Factors/metabolism
Chemicals
Forkhead Transcription Factors Foxf1 protein, mouse Histones Homeodomain Proteins RNA, Long Noncoding Transcription Factors Myeloid-Lymphoid Leukemia Protein homeobox protein PITX2 Histone-Lysine N-Methyltransferase Kmt2a protein, mouse Polycomb Repressive Complex 2
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Grote Phillip
Max Planck Institute for Molecular Genetics, Department of Developmental Genetics, Ihnestr. 63-73, 14195 Berlin, Germany.
Wittler Lars
Hendrix David
Koch Frederic
Währisch Sandra
Beisaw Arica
Macura Karol
Bläss Gaby
Kellis Manolis
Werber Martin
Herrmann Bernhard G
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
DOI
10.1016/j.devcel.2012.12.012
Published
2013-01-28
Pages
206-14
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC4149175
Subset
IM
Grants
NHGRI NIH HHS · R01 HG004037 · United States
NCI NIH HHS · RC1 CA147187 · United States
Databases
GENBANK
JQ973641
GEO
GSE43078
External Links
PubMed source DOI: 10.1016/j.devcel.2012.12.012 PMC Full Text View journal details
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