scholarly journals Local chromatin environment of a Polycomb target gene instructs its own epigenetic inheritance

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Scott Berry ◽  
Matthew Hartley ◽  
Tjelvar S G Olsson ◽  
Caroline Dean ◽  
Martin Howard

Inheritance of gene expression states is fundamental for cells to ‘remember’ past events, such as environmental or developmental cues. The conserved Polycomb Repressive Complex 2 (PRC2) maintains epigenetic repression of many genes in animals and plants and modifies chromatin at its targets. Histones modified by PRC2 can be inherited through cell division. However, it remains unclear whether this inheritance can direct long-term memory of individual gene expression states (cis memory) or instead if local chromatin states are dictated by the concentrations of diffusible factors (trans memory). By monitoring the expression of two copies of the Arabidopsis Polycomb target gene FLOWERING LOCUS C (FLC) in the same plants, we show that one copy can be repressed while the other is active. Furthermore, this ‘mixed’ expression state is inherited through many cell divisions as plants develop. These data demonstrate that epigenetic memory of FLC expression is stored not in trans but in cis.

2014 ◽  
Vol 54 (5) ◽  
pp. 777-790 ◽  
Author(s):  
Nadya Dimitrova ◽  
Jesse R. Zamudio ◽  
Robyn M. Jong ◽  
Dylan Soukup ◽  
Rebecca Resnick ◽  
...  

Genetics ◽  
1992 ◽  
Vol 130 (1) ◽  
pp. 125-138 ◽  
Author(s):  
T Hazelrigg ◽  
S Petersen

Abstract The white gene in the AR4-24 P[white,rosy] insertion on chromosome 2 has a novel expression pattern, in which it is repressed in the dorsal half of the eye. X-ray mutagenesis led to the isolation of six revertants mapping to chromosome 2, which are wild type in a zeste+ background, and three extreme derivatives, in which white gene expression is repressed in ventral regions of the eye as well. By Southern blot analyses the breakpoints of five of the revertants and one of the extreme derivatives were mapped in the flanking DNA bordering each side of the AR4-24 insertion. The revertants show some dorsal repression of white in the presence of z1, and by this criterion each is only a partial revertant. The extreme derivatives act not only in cis, but also in trans to repress expression of AR4-24 and its various derivatives. We provide evidence that these trans effects are proximity-dependent effects, possibly mediated by pairing of gene copies, as they do not extend to copies of the white gene located elsewhere in the genome. We show that one extreme derivative, E1, is a small deletion spanning the insertion site at the 5' end of the white gene, and propose that the distance between a negative regulatory element in the 5' flanking DNA and the white promoter influences the degree of the repression.


2020 ◽  
Vol 117 (21) ◽  
pp. 11459-11470 ◽  
Author(s):  
Qian Bian ◽  
Erika C. Anderson ◽  
Qiming Yang ◽  
Barbara J. Meyer

Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization inCaenorhabditis elegansand investigate roles for compartments in regulating gene expression. Distal arms ofC. eleganschromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other bothin cisandin trans,while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genesmet-2andset-25significantly impaired formation of inactive Arm and active Center compartments.cec-4mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote theircisassociation, and an anchoring-independent mechanism that compacts individual chromosome arms. In bothmet-2 set-25andcec-4mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.


2020 ◽  
Vol 21 (24) ◽  
pp. 9501
Author(s):  
Jun Wang ◽  
Gang Greg Wang

Enhancer of zeste homolog 2 (EZH2) plays critical roles in a range of biological processes including organ development and homeostasis, epigenomic and transcriptomic regulation, gene repression and imprinting, and DNA damage repair. A widely known function of EZH2 is to serve as an enzymatic subunit of Polycomb repressive complex 2 (PRC2) and catalyze trimethylation of histone H3 lysine 27 (H3K27me3) for repressing target gene expression. However, an increasing body of evidence demonstrates that EZH2 has many “non-conventional” functions that go beyond H3K27 methylation as a Polycomb factor. First, EZH2 can methylate a number of nonhistone proteins, thereby regulating cellular processes in an H3K27me3-independent fashion. Furthermore, EZH2 relies on both methyltransferase-dependent and methyltransferase-independent mechanisms for modulating gene-expression programs and/or epigenomic patterns of cells. Importantly, independent of PRC2, EZH2 also forms physical interactions with a number of DNA-binding factors and transcriptional coactivators to context-dependently influence gene expression. The purpose of this review is to detail the complex, noncanonical roles of EZH2, which are generally less appreciated in gene and (epi)genome regulation. Because EZH2 deregulation is prevalent in human diseases such as cancer, there is increased dependency on its noncanonical function, which shall have important implications in developing more effective therapeutics.


2019 ◽  
Vol 63 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Giuseppina Pisignano ◽  
Ioanna Pavlaki ◽  
Adele Murrell

Abstract Chromatin architecture has a significant impact on gene expression. Evidence in the last two decades support RNA as an important component of chromatin structure [Genes Dev. (2005) 19, 1635–1655; PLoS ONE (2007) 2, e1182; Nat. Genet. (2002) 30, 329–334]. Long non-coding RNAs (lncRNAs) are able to control chromatin structure through nucleosome positioning, interaction with chromatin re-modellers and chromosome looping. These functions are carried out in cis at the site of lncRNAs transcription or in trans at distant loci. While the evidence for a role in lncRNAs in regulating gene expression through chromatin interactions is increasing, there is still very little conclusive evidence for a potential role in looping organisation. Here, we review models for the involvement of lncRNAs in genome architecture and the experimental evidence to support them.


2019 ◽  
Vol 47 (12) ◽  
pp. 6396-6410 ◽  
Author(s):  
Hendrik Melior ◽  
Siqi Li ◽  
Ramakanth Madhugiri ◽  
Maximilian Stötzel ◽  
Saina Azarderakhsh ◽  
...  

Abstract Ribosome-mediated transcription attenuation is a basic posttranscriptional regulation mechanism in bacteria. Liberated attenuator RNAs arising in this process are generally considered nonfunctional. In Sinorhizobium meliloti, the tryptophan (Trp) biosynthesis genes are organized into three operons, trpE(G), ppiD-trpDC-moaC-moeA, and trpFBA-accD-folC, of which only the first one, trpE(G), contains a short ORF (trpL) in the 5′-UTR and is regulated by transcription attenuation. Under conditions of Trp sufficiency, transcription is terminated between trpL and trpE(G), and a small attenuator RNA, rnTrpL, is produced. Here, we show that rnTrpL base-pairs with trpD and destabilizes the polycistronic trpDC mRNA, indicating rnTrpL-mediated downregulation of the trpDC operon in trans. Although all three trp operons are regulated in response to Trp availability, only in the two operons trpE(G) and trpDC the Trp-mediated regulation is controlled by rnTrpL. Together, our data show that the trp attenuator coordinates trpE(G) and trpDC expression posttranscriptionally by two fundamentally different mechanisms: ribosome-mediated transcription attenuation in cis and base-pairing in trans. Also, we present evidence that rnTrpL-mediated regulation of trpDC genes expression in trans is conserved in Agrobacterium and Bradyrhizobium, suggesting that the small attenuator RNAs may have additional conserved functions in the control of bacterial gene expression.


2021 ◽  
Author(s):  
Xuan Cai ◽  
Bozeng Tang ◽  
Ahmed Hendy ◽  
Zhiyong Ren ◽  
Caiyun Liu ◽  
...  

SUMMARYBiotrophic and hemibiotrophic fungi have evolved the ability to colonize living plant cells, but how they establish biotrophic growth by remodeling gene expression is poorly understood. By using in planta invasive hyphae (IH) of Magnaporthe oryzae to perform an integrated Chromatin immunoprecipitation sequencing (ChIPseq) and RNA-seq analysis, combining with biological and cellular analyses, we found Polycomb repressive complex 2 (PRC2)-mediated epigenetic repression plays a key role in regulating biotrophic growth. ChIPseq for biotrophic IH samples identified 1701 PRC2 target genes. RNA-seq analysis showed that expression of 462 PRC2 target genes were up-regulated in the Δsuz12 mutant, while 82 were down-regulated, indicating a major role of PRC2 in gene repression of IH. During biotrophic growth, PRC2 repressed fungal cell wall synthesis genes and extracellular enzyme genes required for penetration, and secondary metabolites biosynthesis genes required for necrotrophic growth. A great number of effector-encoding genes were repressed by PRC2, which were highly expressed during penetration stage, suggesting PRC2 coordinates biotrophic growth by regulating effector suppression for immune evasion. This regulation was finely coordinated by Pmk1, through regulating phosphorylation, nuclear localization and protein abundance of Suz12. Our results indicate that the Pmk1-PRC2 regulatory module is required for gene remodeling to facilitate biotrophic growth in M. oryzae.IMPORTANCEBiotrophic and hemibiotrophic fungi establish a biotrophic stage for infection in host cells. For example, M. oryzae forms appressoria to penetrate host cell and establish a biotrophic growth stage for infection. How gene expression patterns are elaborately controlled for fungal biotrophic growth is largely unknown. In this study, we found that, the PRC2-mediated H3K27me3 repressed fungal penetration-required cell wall synthesis genes and extracellular enzyme genes, and necrotrophic growth-required secondary metabolites biosynthesis genes for biotrophic growth. Interestingly, a great number of effector-encoding genes were also repressed by PRC2 at biotrophic stage, which were highly expressed at penetration stage, suggesting PRC2 coordinates biotrophic growth by regulating effector suppression for immune evasion. The PRC2-mediated epigenetic repression is therefore required for the gene expression remodeling during fungal infection. This regulation was finely coordinated by Pmk1, through regulating nuclear localization and protein abundance of the PRC2 component Suz12.


2019 ◽  
Vol 20 (20) ◽  
pp. 5224
Author(s):  
Maciej Dylewski ◽  
Llorenç Fernández-Coll ◽  
Bożena Bruhn-Olszewska ◽  
Carlos Balsalobre ◽  
Katarzyna Potrykus

GreA is a well-characterized transcriptional factor that acts primarily by rescuing stalled RNA polymerase complexes, but has also been shown to be the major transcriptional fidelity and proofreading factor, while it inhibits DNA break repair. Regulation of greA gene expression itself is still not well understood. So far, it has been shown that its expression is driven by two overlapping promoters and that greA leader encodes a small RNA (GraL) that is acting in trans on nudE mRNA. It has been also shown that GreA autoinhibits its own expression in vivo. Here, we decided to investigate the inner workings of this autoregulatory loop. Transcriptional fusions with lacZ reporter carrying different modifications (made both to the greA promoter and leader regions) were made to pinpoint the sequences responsible for this autoregulation, while GraL levels were also monitored. Our data indicate that GreA mediated regulation of its own gene expression is dependent on GraL acting in cis (a rare example of dual-action sRNA), rather than on the promoter region. However, a yet unidentified, additional factor seems to participate in this regulation as well. Overall, the GreA/GraL regulatory loop seems to have unique but hard to classify properties.


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