Functional assessment of CTCF sites at cytokine-sensing mammary enhancers in mammary gland [4C-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE95757 | GEO | 2017/03/24
SECONDARY ACCESSION(S): PRJNA378320
REPOSITORIES: GEO
Similar Datasets
Project description:The zinc finger protein CTCF has been invoked in establishing functional boundaries between genes and thereby controlling enhancer activities. However, there is limited genetic evidence to support such a concept. We have now addressed this question in a locus containing five mammary-specific genes controlled by enhancers. We have identified four CTCF binding sites in the casein locus, two at the outside boundaries and two associated with a super-enhancer. Individual deletions of these sites from the mouse genome did not alter expression of the five casein genes and Odam. However, deletion of the border CTCF site separating the Csn1s1 enhancer from non-mammary genes resulted in the activation of Sult1d1 at a distance of more than 95 kb but not the more proximal Sult1e1 gene. Loss of this CTCF site led to de novo interactions between the Csn1s1 enhancer and the Sult1d1 promoter but not with the silent Sult1e1 gene. Our study suggests that most CTCF sites associated with cell-specific enhancers and super-enhancers have no measurable in vivo activity. Only the loss of one CTCF site led to the induction of a juxtaposed active non-target promoter. Our study also demonstrated that cell-specific enhancers are unable to activate juxtaposed silent non-target promoters.
2017-03-24 | GSE92591 | GEO
Project description:Genetic (animal species, breed and genotype) has a considerable effect on milk composition. In particular, goats present a remarkable polymorphism at the alpha-S1-casein (CSN1S1) locus which results in large differences in milk protein content and indirectly in milk fat content and its fatty acids composition. In order to decipher the mammary metabolic pathways involved, we examined the effect of CSN1S1 polymorphism on the expression of 8,379 genes in caprine mammary gland using a bovine oligonucleotide microarray. Six lactating goats fed ad libitum were assigned to 2 groups based on their genotype at the CSN1S1 locus: High vs. Low genotype goats carrying, respectively, two reference alleles associated with high CSN1S1 synthesis and two defective alleles associated with low CSN1S1 synthesis. Keywords: Genotype comparison
2008-01-03 | GSE6637 | GEO
Project description:Genetic (animal species, breed and genotype) has a considerable effect on milk composition. In particular, goats present a remarkable polymorphism at the alpha-S1-casein (CSN1S1) locus which results in large differences in milk protein content and indirectly in milk fat content and its fatty acids composition. In order to decipher the mammary metabolic pathways involved, we examined the effect of CSN1S1 polymorphism on the expression of 8,379 genes in caprine mammary gland using a bovine oligonucleotide microarray. Six 48-h food-deprived lactating goats were assigned to 2 groups based on their genotype at the CSN1S1 locus: High vs. Low genotype goats carrying, respectively, two reference alleles associated with high CSN1S1 synthesis and two defective alleles associated with low CSN1S1 synthesis. Keywords: Genotype comparison
2008-01-03 | GSE6642 | GEO
Project description:Genetic (animal species, breed and genotype) has a considerable effect on milk composition. In particular, goats present a remarkable polymorphism at the alpha-S1-casein (CSN1S1) locus which results in large differences in milk protein content and indirectly in milk fat content and its fatty acids composition. In order to decipher the mammary metabolic pathways involved, we examined the effect of CSN1S1 polymorphism on the expression of 8,379 genes in caprine mammary gland using a bovine oligonucleotide microarray. Six lactating goats fed ad libitum were assigned to 2 groups based on their genotype at the CSN1S1 locus: High vs. Low genotype goats carrying, respectively, two reference alleles associated with high CSN1S1 synthesis and two defective alleles associated with low CSN1S1 synthesis. Keywords: Genotype comparison 6 slides were performed for a total of 3 independent comparisons (Comp1, Comp2, Comp3): each microarray was co-hybridized with one High CSN1S1 genotype goat sample and one Low CSN1S1 genotype goat sample; each hybridization was repeated in a dye-swap manner for a total of 4 spots per oligonucleotide (2 intra- and 2 inter-slides).
2010-05-27 | E-GEOD-6637 | biostudies-arrayexpress
Project description:Goat's alphaS1-casein (CSN1S1) polymorphism has a significant effect on milk protein and lipid composition, which affects the nutritional quality and technological properties of milk. Moreover, this polymorphism has a large impact on the morphology of mammary epithelial cells. To explore the metabolic pathways modulated in relation to this polymorphism, we compared the mammary gene expression profiles of two groups of lactating goats carrying either two reference or two defective alleles, using a bovine oligonucleotide microarray representing 8379 genes. We identified 41 differentially expressed genes between the two genotype groups. In particular, we showed a downregulation of two key lipogenic genes encoding fatty acid synthase and glycerol-3-phosphate acyltransferase in agreement with the low fat concentration associated with CSN1S1 deficiency. In addition, this study highlights changes in the expression level of several genes known to influence membrane fluidity, cell-cell interaction or chromatin organization. Our results open up new fields of investigation on structural modifications associated with CSN1S1 deficiency that could affect mammary gland function. Keywords: SuperSeries This SuperSeries is composed of the following subset Series: GSE6637: Impact of CSN1S1 polymorphism on mammary transcriptome of lactating goats GSE6642: Impact of CSN1S1 polymorphism on mammary transcriptome of food-deprived lactating goats. Refer to individual Series
2010-05-27 | E-GEOD-6646 | biostudies-arrayexpress
Project description:Genetic (animal species, breed and genotype) has a considerable effect on milk composition. In particular, goats present a remarkable polymorphism at the alpha-S1-casein (CSN1S1) locus which results in large differences in milk protein content and indirectly in milk fat content and its fatty acids composition. In order to decipher the mammary metabolic pathways involved, we examined the effect of CSN1S1 polymorphism on the expression of 8,379 genes in caprine mammary gland using a bovine oligonucleotide microarray. Six 48-h food-deprived lactating goats were assigned to 2 groups based on their genotype at the CSN1S1 locus: High vs. Low genotype goats carrying, respectively, two reference alleles associated with high CSN1S1 synthesis and two defective alleles associated with low CSN1S1 synthesis. Keywords: Genotype comparison 6 slides were performed for a total of 3 independent comparisons (CompA, CompB, CompC): each microarray was co-hybridized with one High CSN1S1 genotype goat sample and one Low CSN1S1 genotype goat sample; each hybridization was repeated in a dye-swap manner for a total of 4 spots per oligonucleotide (2 intra- and 2 inter-slides).
2008-01-02 | E-GEOD-6642 | biostudies-arrayexpress
Project description:Goat's alphaS1-casein (CSN1S1) polymorphism has a significant effect on milk protein and lipid composition, which affects the nutritional quality and technological properties of milk. Moreover, this polymorphism has a large impact on the morphology of mammary epithelial cells. To explore the metabolic pathways modulated in relation to this polymorphism, we compared the mammary gene expression profiles of two groups of lactating goats carrying either two reference or two defective alleles, using a bovine oligonucleotide microarray representing 8379 genes. We identified 41 differentially expressed genes between the two genotype groups. In particular, we showed a downregulation of two key lipogenic genes encoding fatty acid synthase and glycerol-3-phosphate acyltransferase in agreement with the low fat concentration associated with CSN1S1 deficiency. In addition, this study highlights changes in the expression level of several genes known to influence membrane fluidity, cell-cell interaction or chromatin organization. Our results open up new fields of investigation on structural modifications associated with CSN1S1 deficiency that could affect mammary gland function. This SuperSeries is composed of the SubSeries listed below.
2008-01-03 | GSE6646 | GEO
Project description:Precise spatiotemporal regulation of genetic programs, driven by cellspecific super-enhancers, is paramount for the function of cell lineages. Studies have suggested that insulated neighborhoods, formed by the zincfinger protein CTCF, sequester genes and their associated enhancers thus preventing them from trespassing on off-target genes. Although this could explain the enhancer-gene-specificity conundrum, there is limited genetic evidence that the search space of cell-specific super-enhancers is constrained by CTCF. We have addressed this question in the Wap locus with its exceptional mammary-specific super-enhancer, which is separated by five CTCF sites from neighboring genes. Three of these sites are positioned between the Wap super-enhancer and the widely expressed Ramp3. Enhancer deletions demonstrated that the Wap super-enhancer controls Ramp3 expression despite the presence of three parting CTCF sites. Individual and combinatorial deletions of these CTCF sites revealed cell-specific functions of the conserved anchor site. Although unable to block super-enhancer activity, it muffled its impact on Ramp3 in mammary tissue. Unexpectedly, this CTCF site was obligatory for Ramp3 expression in cerebellum, suggesting the coinciding presence of regulatory elements. While our results suggest a surprisingly limited in vivo role for a CTCF anchor in blocking a mammary-specific super-enhancer, they also implicate this site in cerebellum-specific gene activation. Our study illustrates additional complexities of CTCF sites supporting tissue-specific functions.
2017-05-25 | GSE97803 | GEO
Project description:Precise spatiotemporal regulation of genetic programs, driven by cellspecific super-enhancers, is paramount for the function of cell lineages. Studies have suggested that insulated neighborhoods, formed by the zincfinger protein CTCF, sequester genes and their associated enhancers thus preventing them from trespassing on off-target genes. Although this could explain the enhancer-gene-specificity conundrum, there is limited genetic evidence that the search space of cell-specific super-enhancers is constrained by CTCF. We have addressed this question in the Wap locus with its exceptional mammary-specific super-enhancer, which is separated by five CTCF sites from neighboring genes. Three of these sites are positioned between the Wap super-enhancer and the widely expressed Ramp3. Enhancer deletions demonstrated that the Wap super-enhancer controls Ramp3 expression despite the presence of three parting CTCF sites. Individual and combinatorial deletions of these CTCF sites revealed cell-specific functions of the conserved anchor site. Although unable to block super-enhancer activity, it muffled its impact on Ramp3 in mammary tissue. Unexpectedly, this CTCF site was obligatory for Ramp3 expression in cerebellum, suggesting the coinciding presence of regulatory elements. While our results suggest a surprisingly limited in vivo role for a CTCF anchor in blocking a mammary-specific super-enhancer, they also implicate this site in cerebellum-specific gene activation. Our study illustrates additional complexities of CTCF sites supporting tissue-specific functions.
2017-05-25 | GSE92931 | GEO
Project description:Precise spatiotemporal regulation of genetic programs, driven by cellspecific super-enhancers, is paramount for the function of cell lineages. Studies have suggested that insulated neighborhoods, formed by the zincfinger protein CTCF, sequester genes and their associated enhancers thus preventing them from trespassing on off-target genes. Although this could explain the enhancer-gene-specificity conundrum, there is limited genetic evidence that the search space of cell-specific super-enhancers is constrained by CTCF. We have addressed this question in the Wap locus with its exceptional mammary-specific super-enhancer, which is separated by five CTCF sites from neighboring genes. Three of these sites are positioned between the Wap super-enhancer and the widely expressed Ramp3. Enhancer deletions demonstrated that the Wap super-enhancer controls Ramp3 expression despite the presence of three parting CTCF sites. Individual and combinatorial deletions of these CTCF sites revealed cell-specific functions of the conserved anchor site. Although unable to block super-enhancer activity, it muffled its impact on Ramp3 in mammary tissue. Unexpectedly, this CTCF site was obligatory for Ramp3 expression in cerebellum, suggesting the coinciding presence of regulatory elements. While our results suggest a surprisingly limited in vivo role for a CTCF anchor in blocking a mammary-specific super-enhancer, they also implicate this site in cerebellum-specific gene activation. Our study illustrates additional complexities of CTCF sites supporting tissue-specific functions.
2017-05-25 | GSE92587 | GEO