RETRACTED: The Noncoding RNA Mistral Activates Hoxa6 and Hoxa7 Expression and Stem Cell Differentiation by Recruiting MLL1 to Chromatin (Retracted Article)

被引:178
作者
Bertani, Stephane [1 ]
Sauer, Silvia [1 ]
Bolotin, Eugene [2 ]
Sauer, Frank [1 ]
机构
[1] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA
[2] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA
基金
美国国家卫生研究院;
关键词
HISTONE METHYLTRANSFERASE; GENE-EXPRESSION; TARGET GENES; POLYCOMB; PROTEINS; COMPLEXES; PLURIPOTENCY; LEUKEMIA; CLUSTER; ROLES;
D O I
10.1016/j.molcel.2011.08.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The epigenetic activator Mixed lineage leukemia 1 (MLL1) is paramount for embryonic development and hematopoiesis. Here, we demonstrate that the long, noncoding RNA (IncRNA) Mistral (Mira) activates transcription of the homeotic genes Hoxa6 and Hoxa7 in mouse embryonic stem cells (mESC) by recruiting MLL1 to chromatin. The Mira gene is located in the spacer DNA region (SDR) separating Hoxa6 and Hoxa7, transcriptionally silent in mESCs, and activated by retinoic acid. Mira-mediated recruitment of MLL1 to the Mira gene triggers dynamic changes in chromosome conformation, culminating in activation of Hoxa6 and Hoxa7 transcription. Hoxa6 and Hoxa7 activate the expression of genes involved in germ layer specification during mESC differentiation in a cooperative and redundant fashion. Our results connect the IncRNA Mira with the recruitment of MLL1 to target genes and implicate IncRNAs in epigenetic activation of gene expression during vertebrate cell-fate determination.
引用
收藏
页码:1040 / 1046
页数:7
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