MLL2 conveys transcription-independent H3K4 trimethylation in oocytes

Hanna, Courtney W.; Taudt, Aaron; Huang, Joe; Gahurová, Lenka; Kranz, Andrea; Andrews, Simon; Dean, Wendy; Stewart, A. Francis; Colomé-Tatché, Maria; Kelsey, Gavin

doi:10.1038/s41594-017-0013-5

Cited by 134 publications

(192 citation statements)

References 42 publications

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“…In ESCs and oocytes, bivalent genes are usually repressed and hence the absence of Kmt2b causes only a minimal effect on the transcriptome (Denissov et al, 2014;Hanna et al, 2018). To examine whether this is the case in GSCs, we performed RNA-seq analysis and compared the Kmt2bF/F and Kmt2bFC/FC GSC transcriptomes.…”

Section: Bivalent and Monovalent Promoters Are Suppressed By Distinctmentioning

confidence: 99%

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

et al. 2018

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The mammalian male germline is sustained by a pool of spermatogonial stem cells (SSCs) that can transmit both genetic and epigenetic information to offspring. However, the mechanisms underlying epigenetic transmission remain unclear. The histone methyltransferase Kmt2b is highly expressed in SSCs and is required for the SSC-to-progenitor transition. At the stem-cell stage, Kmt2b catalyzes H3K4me3 at bivalent H3K27me3-marked promoters as well as at promoters of a new class of genes lacking H3K27me3, which we call monovalent. Monovalent genes are mainly activated in late spermatogenesis, whereas most bivalent genes are mainly not expressed until embryonic development. These data suggest that SSCs are epigenetically primed by Kmt2b in two distinguishable ways for the upregulation of gene expression both during the spermatogenic program and through the male germline into the embryo. Because Kmt2b is also the major H3K4 methyltransferase for bivalent promoters in embryonic stem cells, we also propose that Kmt2b has the capacity to prime stem cells epigenetically.

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Section: Bivalent and Monovalent Promoters Are Suppressed By Distinctmentioning

confidence: 99%

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

et al. 2018

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“…Importantly, the briefly inherited maternal histone modifications can have important functions. For example, a non-canonical form of maternal H3K4me3 in the mouse oocytes is associated with genome silencing, and its removal is necessary for proper zygotic genome activation (ZGA) (Andreu-Vieyra et al, 2010;Dahl et al, 2016;Hanna et al, 2018;Zhang et al, 2016). Maternal H3K27me3 can be passed on as late as the blastocyst stage (Liu et al, 2016;Zheng et al, 2016), which plays a crucial role in regulating mono-allelic genes, including Xist, a master regulator of X chromosome inactivation (Inoue et al, 2017a(Inoue et al, , 2017b.…”

Section: Introductionmentioning

confidence: 99%

Widespread Enhancer Dememorization and Promoter Priming during Parental-to-Zygotic Transition

Zhang

et al. 2018

Molecular Cell

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“…To validate previously identified maternally methylated imprinted gDMRs (igDMRs) 21–24 , we interrogated DNAme profiles from published whole genome bisulfite sequencing data from gametes, placenta and somatic tissues ( Supplementary Table 1 ) 56 . Specifically, we identified regions that are hypermethylated (> 70% DNAme) in oocytes, hypomethylated (< 30% DNAme) in sperm, retain DNAme (>25%) in the blastocyst, and show 35-65% DNAme in placenta (purified first-trimester cytotrophoblast; CT) or at least one adult somatic tissue 4,5,7,8,18,19,29,40,41,44,47,49,57–69 . We further validated and refined this list by only including gDMRs harboring either reported maternal, monoallelic or bimodal DNAme in the placenta and/or at least one somatic tissue.…”

Section: Methodsmentioning

confidence: 99%

“…3b ). As seen at the Slc38a4 locus, the MTC itself is marked by H3K4me3 44 , and RNA pol II, H3K36me3 and DNAme are enriched over the transcribed region, which encompasses the entire Impact locus, including its igDMR and intronic CGI. Using a CRISPR-Cas9 mutagenesis approach similar to the one described for the MT2A at Slc38a4 , we generated a mouse line in which a ~3 kb region upstream of the Impact gene, including the full-length MTC element, was deleted to generate the Impact MTCKO allele ( Fig.…”

Section: An Upstream Mtc Directs Imprinting At Impactmentioning

confidence: 95%

Evolution of imprinting via lineage-specific insertion of retroviral promoters

Bogutz

Brind’Amour

Kobayashi

et al. 2019

Preprint

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26Imprinted genes are expressed from a single parental allele. In mammals, this unusual mode of 27 transcription generally depends on the epigenetic silencing of one allele by DNA methylation 28 (DNAme) established in the germline. While many species-specific imprinted orthologues have been 29 documented in eutherians, the molecular mechanisms underlying the evolutionary switch from biallelic 30 to imprinted expression are currently unknown. During mouse oogenesis, gametic differentially 31 methylated regions (gDMRs) acquire DNAme in a process guided by transcription. Here we show that 32 transcription initiating in proximal lineage-specific endogenous retroviruses (ERVs) is likely 33 responsible for DNAme established in oocytes at 4/6 mouse-specific and 17/110 human-specific 34 maternal imprinted gDMRs (igDMRs). The latter can be further divided into Catarrhini (Old World 35 monkeys and apes)-or Hominoidea (ape)-specific igDMRs, which are embedded within transcription 36 units initiating in ERVs specific to these primate lineages. Using CRISPR-Cas9 mutagenesis, we 37 deleted the relevant murine-specific ERVs upstream of the maternally methylated genes Impact and 38Slc38a4. Strikingly, imprinting at these genes was lost in the offspring of females harboring these 39 deletions and biallelic expression was observed. Our work reveals a novel evolutionary mechanism 40 whereby maternally silenced genes arise from biallelically expressed progenitors. 41 42 43 During postnatal oocyte growth in mammals, transcribed genomic regions acquire two characteristic 44 epigenetic marks: transcription-coupled trimethylation at lysine 36 of histone H3 (H3K36me3) 1 and 45 DNAme 2-5 . In both human and mouse female germline, the overall levels of CpG methylation increase 46 from less than 5% in post-migratory primordial germ cells (PGCs) to ~40-50% in fully-grown, 47 germinal vesicle oocytes (GVOs) 4,6-8 Kobayashi:2013ia}. In growing murine oocytes, 85-90% of this 48 DNAme is deposited over H3K36me3-marked transcribed regions of the genome 3 . Notably, we 49 recently demonstrated that SETD2-dependent deposition of H3K36me3 is required for de novo 50 3 DNAme of transcribed gene bodies in mouse oocytes 9 . Such transcription-coupled de novo DNAme is 51 also responsible for the establishment of regions of differential DNAme between the mature gametes 52 (gametic differentially methylated regions, gDMRs), a subset of which are maintained throughout 53 preimplantation development. This unique class of gDMRs, the imprinted gDMRs (igDMRs), can 54 direct imprinted paternal allele-specific expression of the gene(s) under their regulation, the imprinted 55 genes 3,10,11 . Importantly, transcription initiating within upstream oocyte-specific promoters has been 56 reported to play a critical role in de novo DNAme at the maternal igDMRs of a number of mouse 57 imprinted genes 3,12-16 , but the evolutionary origin of such promoters remains unexplored. 58 59 Specific families of ERVs, also known as long terminal repeat (LTR) retrotransposons, are 6...

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MLL2 conveys transcription-independent H3K4 trimethylation in oocytes

Cited by 134 publications

References 42 publications

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

Kmt2b conveys monovalent and bivalent H3K4me3 in mouse spermatogonial stem cells at germline and embryonic promoters

Widespread Enhancer Dememorization and Promoter Priming during Parental-to-Zygotic Transition

Evolution of imprinting via lineage-specific insertion of retroviral promoters

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