The Scc2–Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

Lopez-Serra, Lidia; Kelly, Gavin; Patel, Harshil; Stewart, Grant D.; Uhlmann, Frank

doi:10.1038/ng.3080

Cited by 119 publications

(185 citation statements)

References 51 publications

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“…The poly(dA:dT) tract of URA3 plays precisely this role in organizing chromatin (37). The cohesin loading complex (Scc2-Scc4) has been found at A-T rich DNA both in vitro and in vivo (8,38). Together, these findings suggest that the poly(dA:dT) tract helps load functional cohesin complexes that generate cohesion at URA3.…”

Section: Resultsmentioning

confidence: 54%

“…In principle, the A-T rich sequences could act in one of two ways: as a site where functional cohesin complexes are loaded or a site where preloaded, nonfunctional complexes are made competent for cohesion. Recent work showed that the Scc2-Scc4 cohesin loading complex of S. cerevisiae associated with and helped maintain nucleosome free regions like those created by poly(dA:dT) tracts (38). Indeed, the data of LopezSerra et al (38) showed a strong correlation between Scc2-Scc4 binding and the presence of poly(dA:dT) tracts.…”

Section: Discussionmentioning

confidence: 93%

“…Recent work showed that the Scc2-Scc4 cohesin loading complex of S. cerevisiae associated with and helped maintain nucleosome free regions like those created by poly(dA:dT) tracts (38). Indeed, the data of LopezSerra et al (38) showed a strong correlation between Scc2-Scc4 binding and the presence of poly(dA:dT) tracts. Work with proteins purified from S. pombe also showed that both cohesin and the cohesin loading complex possess an affinity toward A-T rich sequences (8).…”

Section: Discussionmentioning

confidence: 93%

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Binding, sliding, and function of cohesin during transcriptional activation

Borrie

Campor

Joshi

et al. 2017

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

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The ring-shaped cohesin complex orchestrates long-range DNA interactions to mediate sister chromatid cohesion and other aspects of chromosome structure and function. In the yeast Saccharomyces cerevisiae, the complex binds discrete sites along chromosomes, including positions within and around genes. Transcriptional activity redistributes the complex to the 3′ ends of convergently oriented gene pairs. Despite the wealth of information about where cohesin binds, little is known about cohesion at individual chromosomal binding sites and how transcription affects cohesion when cohesin complexes redistribute. In this study, we generated extrachromosomal DNA circles to study cohesion in response to transcriptional induction of a model gene, URA3. Functional cohesin complexes loaded onto the locus via a poly(dA:dT) tract in the gene promoter and mediated cohesion before induction. Upon transcription, the fate of these complexes depended on whether the DNA was circular or not. When gene activation occurred before DNA circularization, cohesion was lost. When activation occurred after DNA circularization, cohesion persisted. The presence of a convergently oriented gene also prevented transcription-driven loss of functional cohesin complexes, at least in M phase-arrested cells. The results are consistent with cohesin binding chromatin in a topological embrace and with transcription mobilizing functional complexes by sliding them along DNA.T he protein complex known as cohesin organizes eukaryotic genomes into structures that segregate faithfully between dividing cells. The complex was first discovered for its role in mediating sister chromatid cohesion, but it is now known to participate in numerous aspects of chromosome biology (1, 2). Cohesin is clinically relevant because mutations in subunits of the complex or in factors that load and activate the complex lead to developmental disorders such as Cornelia de Lange syndrome, Roberts syndrome, and Warsaw breakage syndrome (3, 4).Cohesin is a ring-shaped complex composed of four subunits named Smc1, Smc3, Scc3, and Mcd1/Scc1 in budding yeast. The complex is thought to embrace DNA topologically with chromatin fibers passing through a central open channel (5-7). A substantial body of work supports a model in which cohesion arises from single cohesin complexes that embrace both sister chromatids [the double embrace model (6)]. Whether the central channel is large enough to accommodate both chromatids has recently been brought into question (8). In addition, the behavior of cohesin has not always been consistent with a double embrace by single complexes (for examples, see refs. 9-11). These situations usually involve a perturbation that causes loss of cohesion but not a loss of cohesin binding from chromatin. Such results force consideration of alternative models in which cohesin complexes embrace only one chromatid topologically and interact with other cohesin complexes or chromatin features to mediate cohesion (9,11,12).Cohesin binds densely in centromeric regions of chromos...

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Section: Resultsmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 93%

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Binding, sliding, and function of cohesin during transcriptional activation

Borrie

Campor

Joshi

et al. 2017

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

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“…2D,E). This result suggests the possible involvement of the plant cohesinloading complex in sculpting chromatin of interphase nuclei (Lopez-Serra et al, 2014).…”

Section: Expression and Localization Analysis Of Atscc4mentioning

confidence: 70%

The Arabidopsis homolog of Scc4/MAU2 is essential for embryogenesis

Minina

Reza

Gutiérrez-Beltrán

et al. 2017

Journal of Cell Science

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Factors regulating dynamics of chromatin structure have direct impact on expression of genetic information. Cohesin is a multi-subunit protein complex that is crucial for pairing sister chromatids during cell division, DNA repair and regulation of gene transcription and silencing. In non-plant species, cohesin is loaded on chromatin by the Scc2-Scc4 complex (also known as the NIBPL-MAU2 complex). Here, we identify the Arabidopsis homolog of Scc4, which we denote Arabidopsis thaliana (At)SCC4, and show that it forms a functional complex with AtSCC2, the homolog of Scc2. We demonstrate that AtSCC2 and AtSCC4 act in the same pathway, and that both proteins are indispensable for cell fate determination during early stages of embryo development. Mutant embryos lacking either of these proteins develop only up to the globular stage, and show the suspensor overproliferation phenotype preceded by ectopic auxin maxima distribution. We further establish a new assay to reveal the AtSCC4-dependent dynamics of cohesin loading on chromatin in vivo. Our findings define the Scc2-Scc4 complex as an evolutionary conserved machinery controlling cohesin loading and chromatin structure maintenance, and provide new insight into the plant-specific role of this complex in controlling cell fate during embryogenesis.

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“…In budding yeast, cohesin loads onto chromatin at discrete sites (usually heavily-transcribed genes) and then migrates to distal sites where it accumulates (Lengronne et al 2004;Lopez-Serra et al 2014). In the vicinity of HMR, cohesin loading is mediated by the tRNA gene that demarcates the telomere-proximal, silent chromatin boundary (Dubey and Gartenberg 2007).…”

Section: Potential Cell Cycle Regulators Of Silent Chromatin Establismentioning

confidence: 99%

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD + -dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the "nuts and bolts" of silent chromatin and the processes that yield transcriptional silencing.

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The Scc2–Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

Cited by 119 publications

References 51 publications

Binding, sliding, and function of cohesin during transcriptional activation

Binding, sliding, and function of cohesin during transcriptional activation

The Arabidopsis homolog of Scc4/MAU2 is essential for embryogenesis

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

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