Project description:Transposable elements make up nearly half of mammalian genomes, yet are generally described as ‘junk DNA’ or genome parasites. The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, but it is paradoxically expressed at high levels during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem (ES) cells and pre-implantation embryos. In ES cells, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a gene expression program specific to the 2-cell stage. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, thereby promoting rRNA synthesis and ES cell self-renewal. In embryos, LINE1 RNA is required for silencing of Dux, proper synthesis of rRNA and exit from the 2-cell stage. These results reveal an essential partnership between nuclear LINE1 RNA and chromatin factors in the regulation of transcription, developmental potency and ES cell self-renewal.
Project description:Transposable elements make up nearly half of mammalian genomes, yet are generally described as ‘junk DNA’ or genome parasites. The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, but it is paradoxically expressed at high levels during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem (ES) cells and pre-implantation embryos. In ES cells, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a gene expression program specific to the 2-cell stage. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, thereby promoting rRNA synthesis and ES cell self-renewal. In embryos, LINE1 RNA is required for silencing of Dux, proper synthesis of rRNA and exit from the 2-cell stage. These results reveal an essential partnership between nuclear LINE1 RNA and chromatin factors in the regulation of transcription, developmental potency and ES cell self-renewal.
Project description:Transposable elements make up nearly half of mammalian genomes, yet are generally described as ‘junk DNA’ or genome parasites. The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, but it is paradoxically expressed at high levels during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem (ES) cells and pre-implantation embryos. In ES cells, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a gene expression program specific to the 2-cell stage. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, thereby promoting rRNA synthesis and ES cell self-renewal. In embryos, LINE1 RNA is required for silencing of Dux, proper synthesis of rRNA and exit from the 2-cell stage. These results reveal an essential partnership between nuclear LINE1 RNA and chromatin factors in the regulation of transcription, developmental potency and ES cell self-renewal.
Project description:This SuperSeries is composed of the following subset Series: GSE32180: MIWI catalysis is required for piRNA amplification-independent LINE1 transposon silencing [microarray] GSE32184: MIWI catalysis is required for piRNA amplification-independent LINE1 transposon silencing [deep sequencing] Refer to individual Series
Project description:Transposable elements (TEs) are mobile sequences that engender widespread mutations and thus are a major hazard that must be silenced. The most abundant active class of TEs in mammalian genomes is long interspersed element class 1 (LINE1). Here, we report that LINE1 transposition is suppressed in the male germline by transcription factors encoded by a rapidly evolving X-linked homeobox gene cluster. LINE1 transposition is repressed by many members of this RHOX transcription factor family, including those with different patterns of expression during spermatogenesis. One family member—RHOX10—suppresses LINE1 transposition during fetal development in vivo when the germline would otherwise be susceptible to LINE1 activation because of epigenetic reprogramming. We provide evidence that RHOX10 suppresses LINE transposition by inducing Piwil2, which encodes a key component in the Piwi-interacting (pi) RNA pathway that protects against TEs. The ability of RHOX transcription factors to suppress LINE1 is conserved in humans, but is lost in RHOXF2 mutants from several infertile human patients, raising the possibility that loss of RHOXF2 causes human infertility by allowing uncontrolled LINE1 expression in the germline. Together, our results support a model in which the Rhox gene cluster is in an evolutionary arms race with TEs, resulting in expansion of the Rhox gene cluster to suppress TEs in different biological contexts.
Project description:To define short and long-term changes in the phospho-proteome of the cells following Rho-kinase inhibition with H1152 inhibitor, in mouse embryonic fibroblast cells.