Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome

Misulovin, Ziva; Schwartz, Yuri B.; Li, Xiaoyong; Kahn, Tatyana G.; Gause, Maria; MacArthur, Stewart; Fay, Justin C.; Eisen, Michael B.; Pirrotta, Vincenzo; Biggin, Mark D.; Dorsett, Dale

doi:10.1007/s00412-007-0129-1

Cited by 191 publications

(316 citation statements)

References 62 publications

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“…Key roles for cohesin have been shown in a number of cellular processes including DNA repair, 21,22 chromatin modification, 23 DNA condensation 24 and transcriptional regulation in Drosophila, [25][26][27][28] [36][37][38] have demonstrated that the function of Scc2/NIPBL in sister chromatid cohesion is spatially and temporally associated with that of Scc4/MAU2. The C. elegans homolog mau-2 was originally identified for its role in axon guidance 39 and has subsequently been show to have a role in mitotic chromosome segregation.…”

Section: Cdlsmentioning

confidence: 99%

Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

et al. 2011

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Cornelia de Lange syndrome (CdLS; or Brachmann-de Lange syndrome) is a dominantly inherited congenital malformation disorder with features that include characteristic facies, cognitive delays, growth retardation and limb anomalies. Mutations in nearly 60% of CdLS patients have been identified in NIPBL, which encodes a regulator of the sister chromatid cohesion complex. NIPBL, also known as delangin, is a homolog of yeast and amphibian Scc2 and C. elegans PQN-85. Although the exact mechanism of NIPBL function in sister chromatid cohesion is unclear, in vivo yeast and C. elegans experiments and in vitro vertebrate cell experiments have demonstrated that NIPBL/Scc2 functionally interacts with the MAU2/Scc4 protein to initiate loading of cohesin onto chromatin. To test the significance of this model in the clinical setting of CdLS, we fine-mapped the NIPBL-MAU2 interaction domain and tested the functional significance of missense mutations and variants in NIPBL and MAU2 identified in these minimal domains in a cohort of patients with CdLS. We demonstrate that specific novel mutations at the N-terminus of the MAU2-interacting domain of NIPBL result in markedly reduced MAU2 binding, although we appreciate no consistent clinical difference in the small group of patients with these mutations. These data suggest that factors in addition to MAU2 are essential in determining the clinical features and severity of CdLS.

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Section: Cdlsmentioning

confidence: 99%

Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

et al. 2011

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“…Furthermore, when transcription is repressed, cohesin can return (Bausch et al 2007). In flies, cohesin binds to the Abd-B homeobox gene in cells in which it is transcribed, but not in cells in which it is silenced (Misulovin et al 2008). These results emphasize the lack of specificity for any particular DNA sequence, but also highlight that cohesin association with DNA is dynamic, depending on transcription.…”

Section: Introductionmentioning

confidence: 85%

“…The chromosomal sites at which cohesin associates with DNA have been mapped by ChIP-chip (chromatin immunoprecipitation followed by hybridization to DNA microarrays) in yeast, flies, and humans (Glynn et al 2004; Lengronne et al 2004;Misulovin et al 2008;Parelho et al 2008;Stedman 2008;Wendt et al 2008) and by in-situ chromosome staining (McGuinness et al 2005;Gomez et al 2007). These studies revealed both similarities as well as disparities in the localization of cohesin proteins among different eukaryotes.…”

Section: Introductionmentioning

confidence: 99%

“…In budding yeast, cohesin is largely found in regions of convergent transcription and is absent from actively transcribed genes (Glynn et al 2004;Lengronne et al 2004). In contrast, fly cohesin binds preferentially to transcribed regions and overlaps with RNA polymerase II (Misulovin et al 2008). In mammalian cells, most sites are in intergenic regions and introns (Wendt et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…In flies and yeast, there has been no motif significantly associated with the bound sequences (Glynn et al 2004;Lengronne et al 2004;Misulovin et al 2008). In humans, cohesin binding along chromosome arms correlates with a consensus sequence that has been previously identified as the CTCF binding site (Parelho et al 2008;Stedman et al 2008;Wendt et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

McNairn

Gerton

2009

Chromosome Res

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The evolutionarily conserved cohesin proteins Smc1, Smc3, Rad21 (Mcd1), and Scc3 function in the cohesin complex that provides the basis for chromosome cohesion and is involved in gene regulation. Understanding how these proteins link together the genome requires the use of wholegenome approaches to study the molecular mechanisms of these essential proteins. While chromatin immunoprecipitation followed by DNA microarray (ChIP-chip) studies have provided a snapshot in time of where these proteins associate with various genomes, the cohesin proteins are dynamic in their localization and interactions on chromatin. Study of the dynamic nature of these proteins requires approaches such as live cell imaging. We present evidence from fluorescence loss in photobleaching (FLIP) experiments in budding yeast that the decay constant of each cohesin subunit is ∼60-90 s in interphase. The decay constant on chromatin increases from G 1 to S phase to metaphase, consistent with the interaction with chromatin becoming more stable once chromosomes are cohered. A small population of Smc3 at a position consistent with centromeric location has a longer decay constant than bulk Smc3. The characterization of the interaction of cohesin with chromatin, in terms of both its position and its dynamics, may be key to understanding how this protein complex contributes to chromosome segregation and gene regulation.

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Molecular Genetics of Cohesinopathies

Barbero

2014

Encyclopedia of Life Sciences

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Maintenance of sister chromatid cohesion (SCC) until anaphase during cell division is essential for a correct repartition of genetic material to daughter cells. In the search for molecules involved in this process, two independent laboratories have characterised a protein complex, which was denominated the cohesin complex. Although, in the early years, the research focus was on its role in SCC, some years later, new findings have shown that the cohesin complex is involved in several crucial processes in the genome dynamic, deoxyribonucleic acid (DNA) ‐repair, DNA replication and control of transcription and gene expression. The metabolism of cohesin complex and its chromosome interactions are regulated by other proteins, which have been referred as cohesin cofactors or cohesin regulators. Mutations in the cohesin subunits and cohesin cofactor genes, which show a little or no effect in chromosome cohesion, but influence significantly changes in the gene expression, provoke some human pathologies that we know as cohesinopathies. Key Concepts: The protein complex was given the name ‘cohesin’ because it was first characterised in sister chromatid cohesion during chromosome segregation. Cohesin complex function during cell division is essential for correct chromosome segregation to daughter cells and to avoid aneuploidies and tumour formation. Cohesin complex have other important functions apart from chromosome segregation in the genome dynamic, such us DNA‐damage repair, DNA duplication and gene expression control. The role of cohesin complex in gene expression control is essential for right organism development. Cohesin complex functions are also regulated by the cohesin‐interacting proteins named cohesin cofactors or cohesin regulators. Mutations in the genes codifying for cohesin complex subunits and/or cohesin cofactors provoke human syndromes denominated cohesinopathies.

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Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome

Abstract: The cohesin complex is a chromosomal component required for sister chromatid cohesion that is conserved from yeast to man. The similarly conserved Nipped-B protein is needed for cohesin to bind to chromosomes. In higher organisms, Nipped-B and cohesin regulate gene expression and

Cited by 191 publications

References 62 publications

Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

Molecular Genetics of Cohesinopathies

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