Trithorax is required to maintain engrailed expression in a subset of engrailed-expressing cells

Breen, Thomas R.; Chinwalla, Vandana; Harte, Peter J.

doi:10.1016/0925-4773(95)00393-f

Cited by 31 publications

(22 citation statements)

References 48 publications

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“…esc 4 (Q113×) is a null allele resulting from an N-terminal truncation and esc 9 (M236K) is a dominant negative allele (58,59). trx B11 is a null allele resulting from an N-terminal truncation and trx Z11 (G3601S) is a hypomorphic mutation (60)(61)(62)(63). The E(z) 60 trx B11 and the E(z) 60 trx Z11 recombinant flies lines were generated by Thomas Breen.…”

Section: Methodsmentioning

confidence: 99%

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

Siebold¹,

Banerjee²,

Tie³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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177

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Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are key epigenetic regulators of global transcription programs. Their antagonistic chromatin-modifying activities modulate the expression of many genes and affect many biological processes. Here we report that heterozygous mutations in two core subunits of Polycomb Repressive Complex 2 (PRC2), the histone H3 lysine 27 (H3K27)-specific methyltransferase E(Z) and its partner, the H3 binding protein ESC, increase longevity and reduce adult levels of trimethylated H3K27 (H3K27me3). Mutations in trithorax (trx), a well known antagonist of Polycomb silencing, elevate the H3K27me3 level of E(z) mutants and suppress their increased longevity. Like many long-lived mutants, E(z) and esc mutants exhibit increased resistance to oxidative stress and starvation, and these phenotypes are also suppressed by trx mutations. This suppression strongly suggests that both the longevity and stress resistance phenotypes of PRC2 mutants are specifically due to their reduced levels of H3K27me3 and the consequent perturbation of Polycomb silencing. Consistent with this, long-lived E(z) mutants exhibit derepression of Abd-B, a well-characterized direct target of Polycomb silencing, and Odc1, a putative direct target implicated in stress resistance. These findings establish a role for PRC2 and TRX in the modulation of organismal longevity and stress resistance and indicate that moderate perturbation of Polycomb silencing can increase longevity.aging | epigenetics | histone methyltransferase | Polycomb silencing

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Section: Methodsmentioning

confidence: 99%

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

Siebold¹,

Banerjee²,

Tie³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

177

149

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“…en encodes a homeodomain-containing protein important for segmentation in the embryo and formation of posterior compartments in adults. en is regulated by PcG-and Trx-group genes in both embryos and larvae (Moazed and O'Farrell, 1992;McKeon et al, 1994;Breen et al, 1995). We have been studying a multipartite PRE near the en transcription start site (from -2.4 kb to -395 bp) that is bound by PcG proteins in tissue culture cells, embryos and adults (Strutt and Paro, 1997;Négre et al, 2006;Schwartz et al, 2006;Comet et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The role of Polycomb-group response elements in regulation ofengrailedtranscription inDrosophila

et al. 2008

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Polycomb group proteins are required for long-term repression of many genes in Drosophila and all metazoans. In Drosophila, DNA fragments called Polycomb-group response elements (PREs) have been identified that mediate the action of Polycomb-group proteins. Previous studies have shown that a 2 kb fragment located from -2.4 kb to -395 bp upstream of the Drosophila engrailed promoter contains a multipartite PRE that can mediate mini-white silencing and act as a PRE in an Ubx-reporter construct. Here, we study the role of this 2 kb fragment in the regulation of the engrailed gene itself. Our results show that within this 2 kb fragment, there are two subfragments that can act as PREs in embryos. In addition to their role in gene silencing, these two adjacent PRE fragments can facilitate the activation of the engrailed promoter by distant enhancers. The repressive action of the engrailed PRE can also act over a distance. A 181 bp subfragment can act as a PRE and also mediate positive effects in an enhancer-detector construct. Finally, a deletion of 530 bp of the 2 kb PRE fragment within the endogenous engrailed gene causes a loss-of-function phenotype, showing the importance of the positive regulatory effects of this PRE-containing fragment. Our data are consistent with the model that engrailed PREs bring chromatin together, allowing both positive and negative regulatory interactions between distantly located DNA fragments.

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“…Second, particular PP1␤9C functions that are specific for this isoform may be critical in the wing only due to the specificity of the processes involving these functions or the presence of particular PP1c targeting subunits/cofactors. It has been shown that trx is involved in Drosophila wing development by maintaining the normal level of engrailed expression in the posterior wing compartment (Breen et al, 1995); PP1␤9C could modulate this regulation. On the other hand, the wing defects observed in flw; trx/trx mutants may be due to a disrupted trx-dependent regulation of other processes that specifically require PP1␤9C, e.g., indirect flight muscles development or wing cell adhesion (Raghavan et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

PP1β9C interacts with trithorax in Drosophila wing development

Rudenko

Bennett

Alphey

2004

Developmental Dynamics

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Type 1 Ser/Thr protein phosphatase (PP1) has many roles in Drosophila: regulating diverse processes from chromatin condensation to transforming growth factor-␤ signaling. The presence of four PP1 genes, PP1␣87B, PP1␤9C, PP1␣96A, and PP1␣13C, encoding very similar proteins complicates analysis of their particular functions. Here, we report that the minor PP1 isoform PP1␤9C binds in vitro and in vivo and genetically interacts with Trithorax (TRX), the archetypal member of the Trx-G family of epigenetic regulators in Drosophila. Direct binding was demonstrated by GST pull-down experiments and PP1␤9C/TRX interaction in vivo was confirmed by coimmune precipitation from Drosophila embryonic extracts. PP1␤9C was found to be present at all TRX sites on the polytene chromosomes. Flies homo-and hemizygous for loss-of-function alleles of PP1␤9C exhibited specific wing defects when combined with various trx mutants, which indicates that PP1␤9C and TRX cooperate in Drosophila wing development.

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Trithorax is required to maintain engrailed expression in a subset of engrailed-expressing cells

Cited by 31 publications

References 48 publications

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance

The role of Polycomb-group response elements in regulation ofengrailedtranscription inDrosophila

PP1β9C interacts with trithorax in Drosophila wing development

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