UHRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells

Dong, Juan; Wang, Xiaoli; Cao, Congcong; Wen, Yujiao; Sakashita, Akihiko; Chen, Si; Zhang, Jin; Zhang, Yue; Zhou, Li-Quan; Luo, Mengcheng; Liu, Mingxi; Liao, Aihua; Namekawa, Satoshi H.; Yuan, Shuiqiao

doi:10.1038/s41467-019-12455-4

Cited by 69 publications

(74 citation statements)

References 62 publications

(64 reference statements)

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“…Uhrf1 has been shown to interact with PRMT5 (arginine methyltransferase) to catalyze the formation of H4R3me2s and H3R2me2s. These marks also act together with PIWI proteins to facilitate retrotransposon silencing in the germline [47]. We found that H1t-oligonucleosomes associate with Tdkrh, a known interacting protein partner with Uhrf1 and PIWI proteins, further supporting our observations of association of H1t with repressed-repeat element chromatin domains in pachytene spermatocytes.…”

Section: Mass Spectrometric Identification Of Proteins Associated Witsupporting

confidence: 88%

Linker histone variant H1t is closely associated with repressed repeat-element chromatin domains in pachytene spermatocytes

Mahadevan

Kumar²,

2020

Epigenetics & Chromatin

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Background: H1t is the major linker histone variant in pachytene spermatocytes, where it constitutes 50-60% of total H1. This linker histone variant was previously reported to localize in the nucleolar rDNA element in mouse spermatocytes. Our main aim was to determine the extra-nucleolar localization of this linker histone variant in pachytene spermatocytes. Results: We generated H1t-specific antibodies in rabbits and validated its specificity by multiple assays like ELISA, western blot, etc. Genome-wide occupancy studies, as determined by ChIP-sequencing in P20 mouse testicular cells revealed that H1t did not closely associate with active gene promoters and open chromatin regions. Annotation of H1t-bound genomic regions revealed that H1t is depleted from DSB hotspots and TSS, but are predominantly associated with retrotransposable repeat elements like LINE and LTR in pachytene spermatocytes. These chromatin domains are repressed based on co-association of H1t observed with methylated CpGs and repressive histone marks like H3K9me3 and H4K20me3 in vivo. Mass spectrometric analysis of proteins associated with H1t-containing oligonucleosomes identified piRNA-PIWI pathway proteins, repeat repression-associated proteins and heterochromatin proteins confirming the association with repressed repeat-element genomic regions. We validated the interaction of key proteins with H1t-containing oligonucleosomes by use of ChIP-western blot assays. On the other hand, we observe majority of H1t peaks to be associated with the intergenic spacer of the rDNA element, also in association with SINE elements of the rDNA element. Thus, we have identified the genomic and chromatin features of both nucleolar and extranucleolar localization patterns of linker histone H1t in the context of pachytene spermatocytes. Conclusions: H1t-containing repeat-element LINE and LTR chromatin domains are associated with repressive marks like methylated CpGs, histone modifications H3K9me3 and H4K20me3, and heterochromatin proteins like HP1β, Trim28, PIWIL1, etc. Apart from localization of H1t at the rDNA element, we demonstrate the extranucleolar association of this linker histone variant at repeat-associated chromatin domains in pachytene spermatocytes. We hypothesize that H1t might induce local chromatin relaxation to recruit heterochromatin and repeat repression-associated protein factors necessary for TE (transposable element) repression, the final biological effect being formation of closed chromatin repressed structures.

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Section: Mass Spectrometric Identification Of Proteins Associated Witsupporting

confidence: 88%

Linker histone variant H1t is closely associated with repressed repeat-element chromatin domains in pachytene spermatocytes

Mahadevan

Kumar²,

2020

Epigenetics & Chromatin

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“…In addition, a recent study showed that the Ubiquitin-like, Containing PHD and RING finger Domains 1 (UHRF1) protein may interact with MIWI and MILI to deposit DNA methylation or to further recruit PRMT5 to methylate arginine of histones [ 64 ]. This study demonstrated the requirement of UHRF1 in histone and DNA methylation.…”

Section: The Function Of Piwi Proteins and Pirnas In Transposon Silenmentioning

confidence: 99%

Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs

Wang

Lin

2021

Genome Biol

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PIWI proteins, a subfamily of PAZ/PIWI Domain family RNA-binding proteins, are best known for their function in silencing transposons and germline development by partnering with small noncoding RNAs called PIWI-interacting RNAs (piRNAs). However, recent studies have revealed multifaceted roles of the PIWI-piRNA pathway in regulating the expression of other major classes of RNAs in germ cells. In this review, we summarize how PIWI proteins and piRNAs regulate the expression of many disparate RNAs, describing a highly complex global genomic regulatory relationship at the RNA level through which piRNAs functionally connect all major constituents of the genome in the germline.

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“…Nevertheless, there is still progress to further dissect Piwi pathways in Drosophilid spermatogonia such as possible nuclear to cytoplasmic shuttling of PIWI during spermatogonia mitosis [ 85 ]. Overall though, there are much fewer studies discussing piRNA biogenesis in the Drosophila male germline [ 86 , 87 , 88 , 89 , 90 ] compared to the female germline, which we predict may also be the trend in mosquitoes if spermatogenesis development patterns are similar.…”

Section: Genome Transposon Composition and Germline Specificity Ofmentioning

confidence: 88%

Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways

Gamez

Srivastav

Akbari

et al. 2020

Cells

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Animals face the dual threat of virus infections hijacking cellular function and transposons proliferating in germline genomes. For insects, the deeply conserved RNA interference (RNAi) pathways and other chromatin regulators provide an important line of defense against both viruses and transposons. For example, this innate immune system displays adaptiveness to new invasions by generating cognate small RNAs for targeting gene silencing measures against the viral and genomic intruders. However, within the Dipteran clade of insects, Drosophilid fruit flies and Culicids mosquitoes have evolved several unique mechanistic aspects of their RNAi defenses to combat invading transposons and viruses, with the Piwi-piRNA arm of the RNAi pathways showing the greatest degree of novel evolution. Whereas central features of Piwi-piRNA pathways are conserved between Drosophilids and Culicids, multiple lineage-specific innovations have arisen that may reflect distinct genome composition differences and specific ecological and physiological features dividing these two branches of Dipterans. This perspective review focuses on the most recent findings illuminating the Piwi/piRNA pathway distinctions between fruit flies and mosquitoes, and raises open questions that need to be addressed in order to ameliorate human diseases caused by pathogenic viruses that mosquitoes transmit as vectors.

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UHRF1 suppresses retrotransposons and cooperates with PRMT5 and PIWI proteins in male germ cells

Cited by 69 publications

References 62 publications

Linker histone variant H1t is closely associated with repressed repeat-element chromatin domains in pachytene spermatocytes

Linker histone variant H1t is closely associated with repressed repeat-element chromatin domains in pachytene spermatocytes

Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs

Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways

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