Polycomb-repressive complex 1 (PRC1) and PRC2 maintain repression at many developmental genes in mouse embryonic stem cells and are required for early development. However, it is still unclear how they are targeted and how they function. We show that the ability of RING1B, a core component of PRC1, to ubiquitinate histone H2A is dispensable for early mouse embryonic development and much of the gene repression activity of PRC1. Our data support a model in which PRC1 and PRC2 reinforce each other's binding but suggest that the key functions of PRC1 lie beyond the enzymatic capabilities of RING1B.
Mobilization of retrotransposons to new genomic locations is a significant driver of
mammalian genome evolution, but these mutagenic events can also cause genetic
disorders. In humans, retrotransposon mobilization is mediated primarily by proteins
encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in
development. Here we show that TEX19.1, which is induced by developmentally
programmed DNA hypomethylation, can directly interact with the L1-encoded protein
L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1
mobilization. We also show that TEX19.1 likely acts, at least in part, through
promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover,
loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in
pluripotent mouse embryonic stem cells, implying that Tex19.1
prevents de novo retrotransposition in the pluripotent phase of the
germline cycle. These data show that post-translational regulation of L1
retrotransposons plays a key role in maintaining trans-generational genome stability
in mammals.DOI:
http://dx.doi.org/10.7554/eLife.26152.001
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