Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene IncRNA

被引：84

作者：

Scarola, Michele ^{[1
]}

Comisso, Elisa ^{[1
]}

Pascolo, Rhena ^{[1
]}

Chiaradia, Riccardo ^{[1
]}

Maria Marion, Rosa ^{[3
]}

Schneider, Claudio ^{[1
,2
]}

Blasco, Maria A. ^{[3
]}

Schoeftner, Stefan ^{[1
,4
]}

Benetti, Roberta ^{[1
,2
]}

机构：

[1] LNCIB, Canc Epigenet Grp, I-34149 Trieste, Italy

[2] Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy

[3] Spanish Natl Canc Res Ctr CNIO, Telomeres & Telomerase Grp, Madrid 28029, Spain

[4] Univ Trieste, Dept Life Sci, I-34128 Trieste, Italy

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

LONG-NONCODING-RNA; NUCLEAR RECEPTOR GCNF; GENE-EXPRESSION; STEM-CELLS; TRANSCRIPTIONAL NETWORK; REGULATES PLURIPOTENCY; HISTONE MODIFICATION; ANTISENSE; PROTEIN; SOX2;

D O I：

10.1038/ncomms8631

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pseudogene-derived, long non-coding RNAs (lncRNAs) act as epigenetic regulators of gene expression. Here we present a panel of new mouse Oct4 pseudogenes and demonstrate that the X-linked Oct4 pseudogene Oct4P4 critically impacts mouse embryonic stem cells (mESCs) self-renewal. Sense Oct4P4 transcription produces a spliced, nuclear-restricted lncRNA that is efficiently upregulated during mESC differentiation. Oct4P4 lncRNA forms a complex with the SUV39H1 HMTase to direct the imposition of H3K9me3 and HP1 alpha to the promoter of the ancestral Oct4 gene, located on chromosome 17, leading to gene silencing and reduced mESC self-renewal. Targeting Oct4P4 expression in primary mouse embryonic fibroblasts causes the re-acquisition of self-renewing features of mESC. We demonstrate that Oct4P4 lncRNA plays an important role in inducing and maintaining silencing of the ancestral Oct4 gene in differentiating mESCs. Our data introduces a sense pseudogene-lncRNA-based mechanism of epigenetic gene regulation that controls the cross-talk between pseudogenes and their ancestral genes.

引用

页数：13

共 61 条

[1] An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors [J].