Repression of Germline Genes in <i>Caenorhabditis elegans</i> Somatic Tissues by H3K9 Dimethylation of Their Promoters

Rechtsteiner, Andreas; Costello, Meghan Elizabeth; Egelhofer, Thea A.; Garrigues, Jocob M.; Strome, Susan; Petrella, Lisa N.

doi:10.1534/genetics.118.301878

Cited by 29 publications

(47 citation statements)

References 63 publications

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“…RNAi against all 15 TF HTA suppressors failed to significantly suppress the HTA phenotype in lin-13 mutants (Figure 1c). DREAM complex bound loci overlap with only about one third of HPL complex bound loci (Garrigues et al 2015;Goetsch et al 2017;Rechtsteiner et al 2019). This may lead to the misregulation of different subsets of genes in driving the HTA phenotype when each of the complexes is disrupted.…”

Section: Resultsmentioning

confidence: 99%

Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of theCaenorhabditis elegansDREAM Repressor Complex

Cherian¹,

Adams²,

Petrella

2020

G3 Genes|Genomes|Genetics

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Establishment and maintenance of proper gene expression is a requirement for normal growth and development. The DREAM complex in Caenorhabditis elegans functions as a transcriptional repressor of germline genes in somatic cells. At 26°, DREAM complex mutants show increased misexpression of germline genes in somatic cells and High Temperature Arrest (HTA) of worms at the first larval stage. To identify transcription factors required for the ectopic expression of germline genes in DREAM complex mutants, we conducted an RNA interference screen against 123 transcription factors capable of binding DREAM target promoter loci for suppression of the HTA phenotype in lin-54 mutants. We found that knock-down of 15 embryonically expressed transcription factors suppress the HTA phenotype in lin-54 mutants. Five of the transcription factors found in the initial screen have associations with Wnt signaling pathways. In a subsequent RNAi suppression screen of Wnt signaling factors we found that knock-down of the non-canonical Wnt/PCP pathway factors vang-1, prkl-1 and fmi-1 in a lin-54 mutant background resulted in strong suppression of the HTA phenotype. Animals mutant for both lin-54 and vang-1 showed almost complete suppression of the HTA phenotype, pgl-1 misexpression, and fertility defects associated with lin-54 single mutants at 26°. We propose a model whereby a set of embryonically expressed transcription factors, and the Wnt/PCP pathway, act opportunistically to activate DREAM complex target genes in somatic cells of DREAM complex mutants at 26°.

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Section: Resultsmentioning

confidence: 99%

Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of theCaenorhabditis elegansDREAM Repressor Complex

Cherian¹,

Adams²,

Petrella

2020

G3 Genes|Genomes|Genetics

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“…Recent work discovered that a subset of germline specific genes contain H3K9me2 177 peaks at their promoters in N2 L1 progeny (Rechtsteiner et al, 2019). This finding 178…”

Section: Mes-4 Germline Genes Display H3k9me2 At Their Promoter Peaksmentioning

confidence: 98%

“…First, MES-4 343 germline genes should normally be targeted for silencing by H3K9me2 in somatic tissues. It 344 has recently been shown that a subset of germline specific genes contain H3K9me2 at their 345 promoters in L1 larvae, and that these peaks are lost or reduced in the absence of LIN15B 346 (Rechtsteiner et al, 2019). We re-examined the H3K9me2 ChIP-seq dataset from this work 347 and found that the MES-4 germline genes that are ectopically expressed in the somatic 348 tissues of spr-5; met-2 progeny also displayed unique H3K9me2 promoter peaks.…”

mentioning

confidence: 94%

“…In addition to providing transcriptional memory of germline genes between 58 generations in the germline, histone methylation has been implicated in repressing 59 germline transcription in somatic tissues. Recent work in C. elegans has shown that a 60 subset of germline genes have H3K9me2 enrichment at their promoters in somatic tissues 61 (Rechtsteiner et al, 2019). Loss of LIN15B, a transcriptional repressor that is a putative 62 member of the DREAM complex, reduces the enrichment of H3K9me2, leading to the 63 ectopic accumulation of H3K36me3 at gene bodies in somatic tissues (Rechtsteiner et al, 64 2019).…”

Section: Introduction 16mentioning

confidence: 99%

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C. elegansestablishes germline versus soma by balancing inherited histone methylation

Carpenter¹,

Lee²,

Plott

et al. 2020

Preprint

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1In C. elegans, the H3K36 methyltransferase, MES-4, helps establish germ cell fate by 2 maintaining H3K36me2/3 at germline genes between generations. Previously, we showed 3 that the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, 4 reprogram histone methylation at fertilization to prevent the ectopic expression of 5 germline genes in somatic tissues. Together, this indicates that SPR-5 and MET-2 maternal 6reprogramming may antagonize MES-4 to establish germline versus soma. Here, we show 7 that spr-5; met-2 mutant progeny have a severe developmental delay that is associated with 8 the ectopic maintenance of H3K36me2/3 at MES-4 targeted germline genes in somatic 9 tissues, and the ectopic expression of these genes. We further show that the developmental 10 delay and the ectopic expression are dependent upon MES-4. Thus, we propose that SPR-5, 11MET-2, and MES-4 balance inherited histone methylation to establish germline versus 12 soma. Without this balance, the inappropriate transcription of germline genes in somatic 13 tissues causes developmental delay. 14 15

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“…In C. elegans, the DREAM complex alters chromatin structure in the nucleus to transcriptionally repress germline genes in somatic cells (Costello and Petrella 2019;Cui et al 2006;Latorre et al 2015;Petrella et al 2011;Rechtsteiner et al 2019;Unhavaithaya et al 2002;Wang et al 2005;Wu et al 2012). The DREAM complex is completely conserved between mammals and C. elegans, and comprised of eight proteins: E2F-DP heterodimer (EFL-1 & DPL-1), a retinoblastoma-like pocket protein , and a 5-subunit MuvB complex (LIN-9, LIN-37, LIN-52, LIN-53, and the DNA binding subunit LIN-54) (Goetsch et al 2017;Harrison et al 2006;Latorre et al 2015;Sadasivam and DeCaprio 2013).…”

Section: Introductionmentioning

confidence: 99%

Wnt signaling activates gene expression in the absence of theC. elegansDREAM repressor complex in somatic cells

Cherian

2019

Preprint

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Establishment and maintenance of proper gene expression is a requirement for normal growth and development. The DREAM complex in Caenorhabditis elegans functions as a transcriptional repressor of germline genes in somatic cells. At 26°C, DREAM complex mutants show temperature associated increase in misexpression of germline genes in somatic cells and High Temperature Arrest (HTA) of worms at the first larval stage. To identify transcription factors required for the ectopic expression of germline genes in DREAM complex mutants, we conducted an RNA interference screen against 123 transcription factors capable of binding DREAM target promoter loci for suppression of the HTA phenotype in lin-54 mutants. We found 15 embryonically expressed transcription factors that suppress the HTA phenotype in lin-54 mutants. Five of the transcription factors found in the initial screen interact with the Wnt signaling pathways.In a subsequent RNAi suppression screen of Wnt signaling factors we found that knockdown of the non-canonical Wnt/PCP pathway factors vang-1, prkl-1 and fmi-1 in lin-54 mutant background resulted in strong suppression of the HTA phenotype. Animals mutant for both lin-54 and vang-1 showed almost complete suppression of the HTA phenotype, pgl-1 misexpression, and fertility defects associated with lin-54 single mutants at 26°C. We propose a model whereby a set of embryonically expressed transcription factors, and the Wnt/PCP pathway, act opportunistically to activate DREAM complex target genes in somatic cells of DREAM complex mutants at 26°C. 4

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Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters

Cited by 29 publications

References 63 publications

Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of theCaenorhabditis elegansDREAM Repressor Complex

Wnt Signaling Drives Ectopic Gene Expression and Larval Arrest in the Absence of theCaenorhabditis elegansDREAM Repressor Complex

C. elegansestablishes germline versus soma by balancing inherited histone methylation

Wnt signaling activates gene expression in the absence of theC. elegansDREAM repressor complex in somatic cells

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