PIWIL4:piRNA binds nascent LINE1 pre-RNA and recruits SPOCD1, C19ORF84, DNMT3A, DNMT3L, the NURD complex, and the BAF complex

Stable Identifier
R-HSA-9727450
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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PIWIL4:piRNA binds nascent LINE1 pre-RNA and recruits SPOCD1, C19ORF84, DNMT3A, DNMT3L, the NURD complex, and the BAF complex
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In fetal gonocytes undergoing de novo DNA methylation, piRNA-associated PIWIL4 (also called HIWI2 in humans and MIWI2 in mice) associates with complementary nascent RNAs of retroelements such as LINE1 (inferred from mice in Aravin et al. 2007) and with SPOCD1, which interacts with C19ORF84, the DNA methyltransferase DNMT3A, the regulatory subunit DNMT3L, and components of the BAF and NURD chromatin remodelling complexes (Zoch et al. 2024, and inferred from mouse homologs in Zoch et al. 2020, reviewed in Li et al. 2020, Wang and Lin 2021). The roles of the BAF and NURD complexes in transposon silencing are not characterized. In mice, a transposon specific DNA methylase, DNMT3C, is also recruited by SPOCD1, however humans lack an identifiable orthologue of DNMT3C (Zoch et al. 2024).
SPOCD1 iinteracts directly with C19ORF84, which interacts with DNMT3L and with MTA2 of the NURD complex (Zoch et al. 2024). Both SPOCD1 and C19ORF84 are required for de novo DNA methylation of transposable elements, which are sources of piRNAs (Zoch et al. 2024, and inferred from mouse homologs in Zoch et al. 2020).
Transcription of transposable elements during transient genome-wide demethylation during gametogenesis thus leads, via piRNAs, PIWIL4, and SPOCD1, to establishment of DNA methylation at pre-existing and newly transposed elements. In human embryonic stem cells, young LINE1 elements (L1HS, L1PA2) are methylated by DNMTs probably directed by piRNAs (Castro-Diaz et al. 2014). PIWIL4 is observed in nuclei of human male fetal germ cells and piRNAs corresponding to the young LINE1 retroelements L1HS, L1PA2, and L1PA3 are most abundant (Reznik et al. 2019).
Literature References
PubMed ID Title Journal Year
38359823 C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line

Zoch, A, Konieczny, G, Auchynnikava, T, Stallmeyer, B, Rotte, N, Heep, M, Berrens, RV, Schito, M, Kabayama, Y, Schöpp, T, Kliesch, S, Houston, B, Nagirnaja, L, O'Bryan, MK, Aston, KI, Conrad, DF, Rappsilber, J, Allshire, RC, Cook, AG, Tüttelmann, F, O'Carroll, D

Mol Cell 2024
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Inferred From
Piwil4:piRNA binds nascent RNA transcript and recruits Spocd1, Gm52993 (C19orf84), Dnmt3a, Dnmt3c, Dnmt3l, the NURD complex, and the BAF complex (Mus musculus)
Authored
May, B  (2021-04-15)
Reviewed
Bourc'his, D  (2024-05-24)
Fernandes, LP  (2024-05-24)
Created
May, B  (2021-04-16)
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