scholarly journals Paramutation: A Heritable Change in Gene Expression by Allelic Interactions In Trans

2009 ◽  
Vol 2 (4) ◽  
pp. 578-588 ◽  
Author(s):  
Maike Stam
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.


Genetics ◽  
1987 ◽  
Vol 117 (2) ◽  
pp. 173-179
Author(s):  
Gary N Gussin ◽  
Susan Brown ◽  
Karen Matz

ABSTRACT A PRM-cI-lacZ fusion inserted into the b2 region of bacteriophage λ was used to isolate mutations affecting expression of both the λ cI gene and the lacZ gene. One such mutation, a change in the cI initiator codon from AUG to AUA, reduces immunity of a λ prophage to superinfection, and causes a 60-70% reduction in β-galactosidase synthesis, even when repressor is supplied in trans. The effect of the mutation on lacZ gene expression is eliminated in a rho  - bacterial strain, and the mutation has no effect on transcription initiated at PRM in vitro. Therefore, the effects of the mutation are due to premature ρ-dependent termination of transcription in the absence of translation of the cI gene, as if the mutation were a nonsense polar mutation.


Microbiology ◽  
2004 ◽  
Vol 150 (4) ◽  
pp. 1079-1084 ◽  
Author(s):  
Bryn Edwards-Jones ◽  
Paul R. Langford ◽  
J. Simon Kroll ◽  
Jun Yu

Previously, the authors have shown that inactivation of Shigella flexneri yihE, a gene of unknown function upstream of dsbA, which encodes a periplasmic disulphide catalyst, results in a global change of gene expression. Among the severely down-regulated genes are galETKM, suggesting that the yihE mutant, Sh54, may inefficiently produce the UDP-glucose and UDP-galactose required for LPS synthesis. This paper demonstrates that LPS synthesis in Sh54 is impaired. As a result, Sh54 is unable to polymerize host cell actin, due to aberrant localization of IcsA, or to cause keratoconjunctivitis in guinea pigs. Furthermore, Sh54 is more sensitive to some antimicrobial agents, and exhibits epithelial cytotoxicity characteristic of neither wild-type nor dsbA mutants. Supplying galETK in trans restores LPS synthesis and corrects all the defects. Hence, it is clear that the Shigella yihE gene is important not only in regulating global gene expression, as shown previously, but also in virulence through LPS synthesis via regulating the expression of the galETK operon.


2020 ◽  
Author(s):  
Mario Flores ◽  
Ivan Ovcharenko

Abstract Background:Recent studies have drawn attention to transcribed enhancers (trEs) as important regulatory elements of gene expression; however, their characteristics and mechanisms of action remain poorly understood. Results:We profiled the characteristics of trEs and obtained insights into their mechanisms of action. We found that trEs harbor functional duality related to bimodal sequence composition. TrEs are composed of nonoverlapping cores and flanking regions (flanks): cores function as regular enhancers, while flanks transcribe enhancer RNAs (eRNAs) that can potentially regulate the expression of their target genes in trans. Cores are evolutionarily conserved and compact, while flanks are significantly longer. We observed that approximately 25% of eRNAs transcribed from the flanks likely contribute to trans DNA:RNA triple helix formation, while another 10% likely employ classical mechanisms of RNA-based regulation. We found that the majority of human enhancers are not transcribed, and trEs are strikingly different from regular enhancers in their functional characteristics. In addition, we found evidence for trEs exhibiting functional duality in regulatory locus encapsulation (RLE), effectively providing localized control over the spread of gene expression upregulation by trE cores and other locus enhancers. Conclusions:In summary, our results advocate for enhancer transcription being an uncommon mechanism of gene regulation, and the duality of transcribed enhancer function being a product of additive, not overlapping, DNA sequence encryption.


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.


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