Cohesin mediates transcriptional insulation by CCCTC-binding factor

Wendt, Kerstin S.; Yoshida, Koshi; Itoh, Takehiko; Bando, Masashige; Koch, Birgit; Schirghuber, Erika; Tsutsumi, Sadami; Nagae, Genta; Ishihara, Kazuhíko; Mishiro, Tsuyoshi; Yahata, Kazuhide; Imamoto, Fumio; Aburatani, Hiroyuki; Nakao, Mitsuyoshi; Imamoto, Naoko; Maeshima, Kazuhiro; Shirahige, Katsuhiko; Peters, Jan Michael

doi:10.1038/nature06634

Cited by 1,060 publications

(1,286 citation statements)

References 53 publications

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“…In HeLa cells, cohesin binds transgenic chicken HS4, the HS that is functionally related to HS5 in the mammalian b-globin locus. Depletion of both CTCF or cohesin in these cells results in impaired insulator function of this HS, indicating that cohesin may play a role together with CTCF in CH formation (54).…”

Section: Ctcf and Cohesinmentioning

confidence: 92%

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Joining the loops: β‐Globin gene regulation

Noordermeer

Laat

2008

IUBMB Life

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SummaryThe mammalian b-globin locus is a multigene locus containing several globin genes and a number of regulatory elements. During development, the expression of the genes changes in a process called ''switching.'' The most important regulatory element in the locus is the locus control region (LCR) upstream of the globin genes that is essential for high-level expression of these genes. The discovery of the LCR initially raised the question how this element could exert its effect on the downstream globin genes. The question was solved by the finding that the LCR and activate globin genes are in physical contact, forming a chromatin structure named the active chromatin hub (ACH). Here we discuss the significance of ACH formation, provide an overview of the proteins implicated in chromatin looping at the b-globin locus, and evaluate the relationship between nuclear organization and b-globin gene expression. IUBMBIUBMB Life, 60(12): 824-833, 2008

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Section: Ctcf and Cohesinmentioning

confidence: 92%

“…Recently, a strong correlation between binding of CTCF and localization of cohesin to genomic loci was reported (54,55). During replication, the cohesin complex keeps the replicated sister chromatids together by forming a ring structure around the two strands.…”

Section: Ctcf and Cohesinmentioning

confidence: 99%

Joining the loops: β‐Globin gene regulation

Noordermeer

Laat

2008

IUBMB Life

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“…32 Cohesin is recruited to chromatin through its interaction with DNA-binding proteins, including the CCCTCF binding factor (CTCF). 33 It co-occupies up to 90% of CTCF binding sites, 33,34 and some functions initially attributed to CTCF may depend on cohesin. 34 The cohesin-CTCF complex, which assembles in a cell-cycle-dependant 35 and developmentally-regulated 36 manner, can recruit RNA polymerase II to directly promote transcription, 37 and form DNA loop structures to mediate transcriptional insulation 31,34 or connect enhancers with core promoters.…”

Section: Discussionmentioning

confidence: 99%

“…33 It co-occupies up to 90% of CTCF binding sites, 33,34 and some functions initially attributed to CTCF may depend on cohesin. 34 The cohesin-CTCF complex, which assembles in a cell-cycle-dependant 35 and developmentally-regulated 36 manner, can recruit RNA polymerase II to directly promote transcription, 37 and form DNA loop structures to mediate transcriptional insulation 31,34 or connect enhancers with core promoters. 25 Complexed with various other transcription factors, cohesin mediates tissue-specific 30,33 and hormone responsive transcription, 33 as well as the coordinated expression of genes with interrelated functions 38 and multiple genes in clusters.…”

Section: Discussionmentioning

confidence: 99%

Familial skewed X-chromosome inactivation linked to a component of the cohesin complex, SA2

et al. 2011

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The gene dosage inequality between females with two X-chromosomes and males with one is compensated for by X-chromosome inactivation (XCI), which ensures the silencing of one X in every somatic cell of female mammals. XCI in humans results in a mosaic of two cell populations: those expressing the maternal X-chromosome and those expressing the paternal X-chromosome. We have previously shown that the degree of mosaicism (the X-inactivation pattern) in a Canadian family is directly related to disease severity in female carriers of the X-linked recessive bleeding disorder, haemophilia A. The distribution of X-inactivation patterns in this family was consistent with a genetic trait having a co-dominant mode of inheritance, suggesting that XCI choice may not be completely random. To identify genetic elements that could be responsible for biased XCI choice, a linkage analysis was undertaken using an approach tailored to accommodate the continuous nature of the X-inactivation pattern phenotype in the Canadian family. Several X-linked regions were identified, one of which overlaps with a region previously found to be linked to familial skewed XCI. SA2, a component of the cohesin complex is identified as a candidate gene that could participate in XCI through its association with CTCF.

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“…Furthermore, it was found recently that cohesin and CTCF-binding sites have a high degree of overlap, and interacts with each other. 20,[22][23][24] Moreover, often cohesin and CTCF have been found to colocalize at several thousand sites in non-repetitive sequences in the human genome. 22,24,25 In addition to the regulation of gene expression, cohesin has also other important functions: it forms a huge tripartite ring, mediates the sister chromatid cohesion, and facilitates the repair of damaged DNA.…”

Section: Gene Expression and Iq In Trisomy 21mentioning

confidence: 99%

The intellectual disability of trisomy 21: differences in gene expression in a case series of patients with lower and higher IQ

Mégarbané

Noguier²,

Stora

et al. 2013

Eur J Hum Genet

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Trisomy 21 (T21), or Down syndrome (DS), is the most frequent and recognizable cause of intellectual disabilities. The level of disability, as evaluated by the intelligence quotient (IQ) test, varies considerably between patients independent of other factors. To determine the genetic or molecular basis of this difference, a high throughput transcriptomic analysis was performed on twenty T21 patients with high and low IQ, and 10 healthy controls using Digital Gene Expression. More than 90 millions of tags were sequenced in the three libraries. A total of 80 genes of potential interest were selected for the qPCR experiment validation, and three housekeeping genes were used for normalizing purposes. HLA DQA1 and HLA DRB1 were significantly downregulated among the patients with a low IQ, the values found in the healthy controls being intermediate between those noted in the IQ þ and IQ À T21 patients. Interestingly, the intergenic region between these genes contains a binding sequence for the CCCTC-binding factor, or CTCF, and cohesin (a multisubunit complex), both of which are essential for expression of HLA DQA1 and HLA DRB1 and numerous other genes. Our results might lead to the discovery of genes, or genetic markers, that are directly involved in several phenotypes of DS and, eventually, to the identification of potential targets for therapeutic interventions.

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Cohesin mediates transcriptional insulation by CCCTC-binding factor

Cited by 1,060 publications

References 53 publications

Joining the loops: β‐Globin gene regulation

Joining the loops: β‐Globin gene regulation

Familial skewed X-chromosome inactivation linked to a component of the cohesin complex, SA2

The intellectual disability of trisomy 21: differences in gene expression in a case series of patients with lower and higher IQ

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