Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved

Rhodes, Jenny M.; Bentley, Fiona K.; Print, Cristin G.; Dorsett, Dale; Misulovin, Ziva; Dickinson, Emma; Crosier, Kathryn E.; Crosier, Philip S.; Horsfield, Julia A.

doi:10.1016/j.ydbio.2010.05.493

Cited by 93 publications

(139 citation statements)

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“…The expression of Myc and cohesin is positively correlated in biological systems ranging from flies to humans (Rhodes et al 2010). Exceptions include resting thymocytes (where Myc expression is low and not affected by cohesin depletion) (Seitan et al 2013), fibroblasts deficient in the cohesin unloading factor Wapl (which show increased cohesin association with chromatin yet fail to up-regulate Myc in response to activation with growth factors) (Tedeschi et al 2013), and ES cells acutely depleted of cohesin under 2i conditions (this study).…”

Section: Cohesin Myc Dna Replication and Reprogrammingmentioning

confidence: 89%

Initiation and maintenance of pluripotency gene expression in the absence of cohesin

et al. 2015

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Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin's contribution to reprogramming in systems that reactivate the expression of pluripotency genes in the absence of proliferation (embryonic stem [ES] cell heterokaryons) or DNA replication (nuclear transfer). Contrary to expectations, cohesin depletion enhanced the ability of ES cells to initiate somatic cell reprogramming in heterokaryons. This was explained by increased c-Myc (Myc) expression in cohesin-depleted ES cells, which promoted DNA replicationdependent reprogramming of somatic fusion partners. In contrast, cohesin-depleted somatic cells were poorly reprogrammed in heterokaryons, due in part to defective DNA replication. Pluripotency gene induction was rescued by Myc, which restored DNA replication, and by nuclear transfer, where reprogramming does not require DNA replication. These results redefine cohesin's role in pluripotency and reveal a novel function for Myc in promoting the replication-dependent reprogramming of somatic nuclei.

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Section: Cohesin Myc Dna Replication and Reprogrammingmentioning

confidence: 89%

Initiation and maintenance of pluripotency gene expression in the absence of cohesin

et al. 2015

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“…Cohesins have been shown to both positively and negatively regulate transcription (11,47,61,67), and more recently, they have been implicated in the control of RNA Pol II pausing (18,33). The transcriptional effects of cohesins may be related to other biochemical properties, including functions associated with chromatin boundaries, insulators, and DNA looping.…”

Section: Discussionmentioning

confidence: 99%

Cohesins Repress Kaposi's Sarcoma-Associated Herpesvirus Immediate Early Gene Transcription during Latency

Chen

Wikramasinghe

Showe

et al. 2012

J Virol

114

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Chromatin-organizing factors such as CTCF and cohesins have been implicated in the control of complex viral regulatory programs. We investigated the role of CTCF and cohesins in the control of the switch from latency to the lytic cycle for Kaposi's sarcoma-associated herpesvirus (KSHV). We found that cohesin subunits but not CTCF are required for the repression of KSHV immediate early gene transcription. Depletion of the cohesin subunits Rad21, SMC1, and SMC3 resulted in lytic cycle gene transcription and viral DNA replication. In contrast, depletion of CTCF failed to induce lytic transcription or DNA replication. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-Seq) revealed that cohesins and CTCF bound to several sites within the immediate early control region for ORF50 and to more distal 5′ sites that also regulate the divergently transcribed ORF45-ORF46-ORF47 gene cluster. Rad21 depletion led to a robust increase in ORF45, ORF46, ORF47, and ORF50 transcripts, with similar kinetics to that observed with chemical induction by sodium butyrate. During latency, the chromatin between the ORF45 and ORF50 transcription start sites was enriched in histone H3K4me3, with elevated H3K9ac at the ORF45 promoter and elevated H3K27me3 at the ORF50 promoter. A paused form of RNA polymerase II (Pol II) was loosely associated with the ORF45 promoter region during latency but was converted to an active elongating form upon reactivation induced by Rad21 depletion. Butyrate treatment caused a rapid dissociation of cohesins and loss of CTCF binding at the immediate early gene locus, suggesting that cohesins may be a direct target of butyrate-mediated lytic induction. Our findings implicate cohesins as a major repressor of KSHV lytic gene activation and show that they function coordinately with CTCF to regulate the switch between latent and lytic gene activity.

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“…In murine embryonic stem cells, cohesin and mediator, a transcriptional co-activator, facilitate DNA looping between the enhancers and promoters of genes required to maintain pluripotency (Kagey et al, 2010). Cohesin also positively regulates the expression of genes such as Myc and the protocadherins (Monahan et al, 2012;Rhodes et al, 2010). Of the two versions of cohesin present in somatic cells, cohesin-SA1 and cohesin-SA2, the former appears to play a more important role in the regulation of gene expression.…”

Section: Cohesin and Transcriptionmentioning

confidence: 99%

Cohesin in development and disease

2013

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SummaryCohesin is a ring-shaped complex, conserved from yeast to human, that was named for its ability to mediate sister chromatid cohesion. This function is essential for chromosome segregation in both mitosis and meiosis, and also for DNA repair. In addition, more recent studies have shown that cohesin influences gene expression during development through mechanisms that likely involve DNA looping and interactions with several transcriptional regulators. Here, we provide an overview of how cohesin functions, highlighting its role both in development and in disease. Key words: Chromatin loops, Cohesion, Cohesinopathies IntroductionThe development of a complex multicellular organism from the fusion of two haploid cells requires two fundamental processes:one is cell proliferation, in order to grow; the other is cell differentiation, in order to generate specialized cells for tissues and organs. The cohesin complex plays key roles in both these processes. Cohesin was originally identified as the mediator of sister chromatid cohesion. It establishes a physical link between the two sister chromatids from the moment they arise from the replication fork. This link is essential for efficient DNA repair by homologous recombination during S/G2, and for proper chromosome alignment and segregation in mitosis. In this way, cohesin ensures the accurate transmission of genetic material during cell proliferation. Regarding cell differentiation, it is clear that what defines a cell type is not its genome, but how this genome is used. Increasing evidence supports the importance of higher order chromatin structure in the temporal and spatial regulation of transcription. We are only beginning to understand how the spatial organization of chromatin affects gene expression, but cohesin is emerging as an important contributor to such organization. Here, and in the accompanying poster, we briefly review our current knowledge of cohesin and its different functions, and focus on how these functions contribute to embryonic development. Development 140, 3715-3718 (2013) DEVELOPMENT 3716The cohesin complex Cohesin consists of four subunits -Smc1, Smc3, Scc1/Rad21 and Scc3/SA -arranged in a ring-shaped structure. Smc1 and Smc3 belong to the structural maintenance of chromosomes (SMC) family of chromosomal ATPases that also includes the core subunits of condensin and of the Smc5/6 complex. These complexes are conserved from yeast to human, and SMC-like proteins contribute to chromosome organization and dynamics in bacteria and archaea (Hirano, 2005). Scc1/Rad21 belongs to the kleisin protein family and interacts with both Smc1 and Smc3 to close the ring. The Scc3/SA subunit in somatic vertebrate cells can be either SA1 or SA2, although additional variants for SA and other subunits also exist in meiotic cells.The regulation of cohesin during the cell cycle Cohesin topologically embraces chromatin fiber(s) within its ringshaped structure (Nasmyth, 2011). The complex is recruited to chromatin during G1 in a process that requires the cohesini...

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Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved

Cited by 93 publications

References 61 publications

Initiation and maintenance of pluripotency gene expression in the absence of cohesin

Initiation and maintenance of pluripotency gene expression in the absence of cohesin

Cohesins Repress Kaposi's Sarcoma-Associated Herpesvirus Immediate Early Gene Transcription during Latency

Cohesin in development and disease

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