The H3K9 methyltransferase SETDB1 maintains female identity in Drosophila germ cells

Smolko, Anne E.; Shapiro-Kulnane, Laura; Salz, Helen K.

doi:10.1038/s41467-018-06697-x

Cited by 50 publications

(94 citation statements)

References 71 publications

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“…These findings suggested that egg does not regulate the pericentric heterochromatin. Further analysis demonstrated that egg is also required in both the soma and germline for the completion of oogenesis (Clough et al 2007(Clough et al , 2014Wang et al 2011;Smolko et al 2018). Egg plays a major role in the piRNA pathway that silences transposons in the germline (Rangan et al 2011;Sienski et al 2015;Yu et al 2015).…”

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confidence: 99%

Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila

2019

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Acquisition of chromatin modifications during embryogenesis distinguishes different regions of an initially naïve genome. In many organisms, repetitive DNA is packaged into constitutive heterochromatin that is marked by di/ trimethylation of histone H3K9 and the associated protein HP1a. These modifications enforce the unique epigenetic properties of heterochromatin. However, in the early Drosophila melanogaster embryo, the heterochromatin lacks these modifications, which appear only later, when rapid embryonic cell cycles slow down at the midblastula transition (MBT). Here we focus on the initial steps restoring heterochromatic modifications in the embryo. We describe the JabbaTrap, a technique for inactivating maternally provided proteins in embryos. Using the JabbaTrap, we reveal a major requirement for the methyltransferase Eggless/SetDB1 in the establishment of heterochromatin. In contrast, other methyltransferases contribute minimally. Live imaging reveals that endogenous Eggless gradually accumulates on chromatin in interphase but then dissociates in mitosis, and its accumulation must restart in the next cell cycle. Cell cycle slowing as the embryo approaches the MBT permits increasing accumulation and action of Eggless at its targets. Experimental manipulation of interphase duration shows that cell cycle speed regulates Eggless. We propose that developmental slowing of the cell cycle times embryonic heterochromatin formation.

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confidence: 99%

Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila

2019

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“…It is required at multiple stages of oogenesis, maintenance and differentiation of Germline and Follicle Stem Cells. It is involved in piRNA cluster transcription and Dpp (Decapentaplegic) signalling during oogenesis, expression of specific long non-coding RNAs, apoptosis-related gene regulation, and silencing of key spermatogenesis gene Phf7 [41,42,43]. The gene eggless along with the sxl (sex determining) gene preserves the female fate by conferring the repressive mark H3K9me3 on Phf7 gene, a histone reader that associates with H3K4me2 and pilots the male sexual program in the germ line [44].…”

Section: Retrieval Of Curated Methylases and Demethylases Orthoclustersmentioning

confidence: 99%

A comparative analysis of histone methyltransferases and demethylases in insect genome: A meta-analysis

Gulati

Kohli

Narang

et al. 2019

Preprint

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Abbreviations: KMT-lysine methyltransferases, PRMT-Protein arginine methyltransferases, PTM-post-translational modification, DSB-double strand break Abstract Background: The epigenetic regulation through post-translational modification of histones, especially methylation is well conserved, while DNA methylation is variable, being very low or absent in Drosophila melanogaster. Though there are several insect genomes sequenced, an analysis with a focus on their epigenetic repertoire is limited. We have compared the histone methyltransferases and the demethylases in the genome of Drosophila melanogaster, Aedes aegypti (Diptera), the pea aphid Acyrthosiphon pisum, the triatomid bug Rhodnius prolixus (Hemiptera), the honeybee Apis mellifera (Hymenoptera), the silkworm Bombyx mori (Lepidoptera) and the red flour beetle Tribolium castaneum (Coleoptera). Results:We identified 38 clusters consisting of arginine, lysine methyltransferases and demethylases using OrthoFinder. To eliminate false positives, we designed a method based on identifying highly conserved domain within each class designated as the high priority domain. Out of the 9 arginine methyltransferases, Art2, Art6 and Art9 are identified in D.melanogaster only. We observe copy number variation between the genomes; A.pisum has nine copies of eggless gene (H3K9me3 methyltransferase), which can be correlated with the switch between parthenogenesis and sexual reproduction. Other than the high-priority domains, these proteins contain shared and unique domains that can mediate protein-protein interaction. Phylogenetic analysis indicates that the there is a broad conservation within the members of a class while duplication and divergence is observed in LSD1. Conclusion:This meta-analysis provides a method for reliable identification of epigenetic modifiers of histones in newly sequenced insect genomes. Similar approach can be taken for other classes of genes.Drome: Drosophila melanogaster, Aedae: Aedes aegypti, Acypi: Acyrthosiphon pisum, Rhopr:Rhodnius prolixus, Apime: Apis mellifera, Bommo: Bombyx mori, Trica: Tribolium castaneum.Art9 is identified only in D. melanogaster and the two isoforms (99.2% identity), were grouped into two singleton clusters as additional 53 amino acids are present at the N-terminal in one of them. As

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“…In the Drosophila ovary, loss of H3K9me3 leads to up-regulation of testis-specific transcripts that change the fate of ovarian germ cells, leading to sterility (Smolko et al 2018). As in C. elegans, prior investigations of H3K9 methylation loss in Drosophila had focused primarily on up-regulation of repetitive elements (Rangan et al 2011;Wang et al 2011;Guo et al 2015;Zeller et al 2016).…”

Section: Repression Of Germline Gene Expression In the Soma Is Vitalmentioning

confidence: 99%

LIN-15B promotes enrichment of H3K9me2 on the promoters of a subset of germline genes that are repressed in somatic cells in C. elegans

Rechtsteiner

Costello

Egelhofer

et al. 2018

Preprint

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Running title: H3K9me2 on synMuv B target genesABSTRACT Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B, lin-35, and lin-37, all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a complex member. We found that in wild-type worms synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9(H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are distributed across the autosomes and not biased toward autosomal arms like broad H3K9me2 domains.Both synMuv B targets and germline genes display dramatic reduction of H3K9me2 promoter localization in lin-15B mutants, but much weaker reduction in lin-35 and lin-37 mutants. This is the first major difference reported between lin-15B and DREAM complex mutants, which likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes through LIN-15B, global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high temperature larval arrest and ectopic expression of germline genes in the soma. We propose that LIN-15B-driven enrichment of H3K9me2 on promoters of germline genes contributes to repression of those genes in somatic tissues.

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The H3K9 methyltransferase SETDB1 maintains female identity in Drosophila germ cells

Cited by 50 publications

References 71 publications

Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila

Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila

A comparative analysis of histone methyltransferases and demethylases in insect genome: A meta-analysis

LIN-15B promotes enrichment of H3K9me2 on the promoters of a subset of germline genes that are repressed in somatic cells in C. elegans

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