National Center for Biotechnology Information , U. Remarkably, long before piRNAs and their roles in protecting germ cell genomes were discovered, the flamenco locus, which is now known as one of the major Drosophila piRNA clusters, was identified genetically as a regulator of gypsy family transposons 10 , A germline-specific class of small RNAs binds mammalian Piwi proteins. Indeed, the first in vitro systems that recapitulate aspects of the pathway have now been established 57 , Interestingly, Mael is not exclusively nuclear but rather shuttles between the nucleus and cytoplasm or nuage  , suggesting a more complex role or even multiple functions.
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Unlike Arx or Panx mutants, cells depleted of Mael show no reduction of H3K9me3 levels but rather spreading of this mark into downstream regions.
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Cleavage immediately upstream of a U nucleotide would further reinforce the 1U bias of phased primary piRNAs produced downstream. Numerous pseudo-genes are known targets of piRNA-mediated silencing, with a prominent example being the interaction between Stellate and Su Ste , which led to the discovery of piRNAs . In addition, Lysine-specific demethylase 1 Lsd1 likely removes active histone 3 lysine 4 dimethylation H3K4me2 marks from transposon promoter regions, leading to efficient suppression of transposons at the transcriptional level.