Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome

Ben-Elazar, Shay; Yakhini, Zohar; Yanai, Itai

doi:10.1093/nar/gks1360

Cited by 52 publications

(58 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, the interaction between the GAL1 reporters was only detected under the activating condition. This observation is consistent with previous statistical analysis, indicating that coregulated genes tend to cluster, and genes that are physically proximal tend to coexpress (21,31,32). Coactivated genes can also form "transcription factories" or "multigene complexes" in higher eukaryotic species (33,34), so our findings here are likely to be one example of a more general phenomenon.…”

Section: Discussionsupporting

confidence: 92%

Interallelic interaction and gene regulation in budding yeast

Zhang

Bai

2016

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

View full text Add to dashboard Cite

In Drosophila, homologous chromosome pairing leads to "transvection," in which the enhancer of a gene can regulate the allelic transcription in trans. Interallelic interactions were also observed in vegetative diploid budding yeast, but their functional significance is unknown. Here, we show that a GAL1 reporter can interact with its homologous allele and affect its expression. By ectopically inserting two allelic reporters, one driven by wild-type GAL1 promoter (WT GAL1pr) and the other by a mutant promoter with delayed response to galactose induction, we found that the two reporters physically associate, and the WT GAL1pr triggers synchronized firing of the defective promoter and accelerates its activation without affecting its steady-state expression level. This interaction and the transregulatory effect disappear when the same reporters are located at nonallelic sites. We further demonstrated that the activator Gal4 is essential for the interallelic interaction, and the transregulation requires fully activated WT GAL1pr transcription. The mechanism of this phenomenon was further discussed. Taken together, our data revealed the existence of interallelic gene regulation in yeast, which serves as a starting point for understanding long-distance gene regulation in this genetically tractable system. homologous pairing | interallelic interaction | interallelic regulation | transvection | single-cell gene expression

show abstract

Section: Discussionsupporting

confidence: 92%

Interallelic interaction and gene regulation in budding yeast

Zhang

Bai

2016

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

View full text Add to dashboard Cite

show abstract

“…Thus, domain formation could ensure similar firing times because clustered origins would then share similar concentrations of replication factors. More broadly, colocalization of transcription and replication factors suggests that spatial clustering is a widely used mechanism to enrich local enzyme concentrations to increase the efficiency of multistep biochemical reactions (52)(53)(54).…”

Section: Discussionmentioning

confidence: 99%

Form and function of topologically associating genomic domains in budding yeast

Eser

Chandler-Brown

et al. 2017

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

View full text Add to dashboard Cite

The genome of metazoan cells is organized into topologically associating domains (TADs) that have similar histone modifications, transcription level, and DNA replication timing. Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity. Furthermore, these boundaries separate regions of similarly timed replication origins connecting the longknown effect of genomic context on replication timing to genome architecture. To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing. Forkhead factors do not regulate TAD formation, but do promote longer-range genomic interactions and control interactions between origins near the centromere. Thus, our work defines spatial organization within the budding yeast nucleus, demonstrates the conserved role of genome architecture in regulating DNA replication, and identifies a molecular mechanism specifically regulating interactions between pericentric origins. A n important distinction between eukaryotic and prokaryotic cells is the presence of the eukaryotic nucleus, which compartmentalizes the cell. It is becoming increasingly clear that the eukaryotic nuclear compartment contains additional layers of spatial organization, including the nucleolus, splicing bodies, transcriptional foci, and the peripheral localization of telomeres (1, 2). In addition, high-throughput chromosome conformation capture (Hi-C) technologies have recently revealed the spatial organization of chromatin into topologically associating domains (TADs) on the 100-kb to 1-Mb scale for mammals (3, 4), as well as the fly Drosophila melanogaster (5), the worm Caenorhabditis elegans (6), and the fission yeast Schizosaccharomyces pombe (7). Loci within a TAD are much more likely to interact with one another than with loci outside the domain (5,8,9).In metazoans, topological domains play important roles in coordinating the DNA-templated processes of replication and transcription (10-12). Chromatin within a TAD tends to have similar histone modifications, and consequently euchromatic or heterochromatic state, so that the genome is organized into self-associated globules that are either permissive or repressive of transcription. Repressive TADs are likely to be associated with the nuclear periphery (8). In addition to coordinating transcription, TADs also coordinate replication so that replication origins within a domain activate synchronously.That TAD nuclear organization is important for transcription and replication has motivated much recent work on the molecular mechanisms underlying TAD formation. The...

show abstract

“…Is it simply a question of depth of sequencing of the ligation products, or does the answer lie in the incorporation and analysis of in silico reconstructions or forward predictive models. Reconstructions of varying complexity have already been generated, 7 , 11 , 16 , 21 , 37 and the analyses of these models is complex. Predictive models can be used to ask different questions and could be generated beginning with ensembles of polymer models that recapitulate the random unpacking of DNA within the nucleus 21 , 69 .…”

Section: Resultsmentioning

confidence: 99%

The statistical-mechanics of chromosome conformation capture

O’Sullivan

Hendy

Pichugina

et al. 2013

Nucleus

View full text Add to dashboard Cite

Since Jacob and Monod’s characterization of the role of DNA elements in gene control, it has been recognized that the linear organization of genome structure is important for the regulation of gene transcription and hence the manifestation of phenotypes. Similarly, it has long been hypothesized that the spatial organization (in three dimensions evolving through time), as part of the epigenome, makes a significant contribution to the genotype-phenotype transition. Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC, and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype. The apparent simplicity of these methodologies—crosslink chromatin, digest, dilute, ligate, detect interactions—belies the complexity of the data and the considerations that should be taken into account to ensure the generation and accurate interpretation of reliable data. Here we discuss the probabilistic nature of these methodologies and how this contributes to their endogenous limitations.

show abstract

Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome

Cited by 52 publications

References 39 publications

Interallelic interaction and gene regulation in budding yeast

Interallelic interaction and gene regulation in budding yeast

Form and function of topologically associating genomic domains in budding yeast

The statistical-mechanics of chromosome conformation capture

Contact Info

Product

Resources

About