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Functional analysis of CTCF sites associated with cytokine-sensing mammary-specific enhancers in the complex casein locus

ABSTRACT: Functional analysis of CTCF sites associated with cytokine-sensing mammary-specific enhancers in the complex casein locus

PROVIDER: PRJNA378301 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5120890.fastq.gz	Fastqsanger.gz
	SRR5120900.fastq.gz	Fastqsanger.gz
	SRR5120891.fastq.gz	Fastqsanger.gz
	SRR5120892.fastq.gz	Fastqsanger.gz
	SRR5120893.fastq.gz	Fastqsanger.gz

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Functional analysis of CTCF sites associated with cytokine-sensing mammary-specific enhancers in the complex casein locus [ChIP-seq]

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

Functional assessment of CTCF sites at cytokine-sensing mammary enhancers in mammary gland [4C-seq]

Project description:In mammary gland, deletion of the border CTCF site separating the Csn1s1 mammary enhancer from neighboring genes resulted in the activation of Sult1d1 at a distance of more than 95 kb but not the more proximal and silent Sult1e1 gene. Loss of this CTCF site led to de novo interactions between the Sult1d1 promoter and several enhancers in the casein locus.

2017-03-24 | GSE95757 | GEO

Functional analysis of CTCF sites associated with cytokine-sensing mammary-specific enhancers in the complex casein locus

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-24 | GSE95758 | GEO

Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer

Project description:Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer

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Cytokine-sensing primary enhancer cluster launches secondary enhancers to activate multi-gene locus

Project description:Cytokine-sensing primary enhancer cluster launches secondary enhancers to activate multi-gene locus

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Functional assessment of CTCF sites at cytokine-sensing mammary enhancers using CRISPR/Cas9 gene editing in mice.

Project description:The zinc finger protein CTCF has been invoked in establishing boundaries between genes, thereby controlling spatial and temporal enhancer activities. However, there is limited genetic evidence to support the concept that these boundaries restrict the search space of enhancers. We have addressed this question in the casein locus containing five mammary and two non-mammary genes under the control of at least seven putative enhancers. We have identified two CTCF binding sites flanking the locus and two associated with a super-enhancer. Individual deletion of these sites from the mouse genome did not alter expression of any of the genes. However, deletion of the border CTCF site separating the Csn1s1 mammary enhancer from neighboring genes resulted in the activation of Sult1d1 at a distance of more than 95 kb but not the more proximal and silent Sult1e1 gene. Loss of this CTCF site led to de novo interactions between the Sult1d1 promoter and several enhancers in the casein locus. Our study demonstrates that only one out of the four CTCF sites in the casein locus had a measurable in vivo activity. Studies on additional loci are needed to determine the biological role of CTCF sites associated with enhancers.

| S-EPMC5416830 | biostudies-literature

Cytokine-sensing primary enhancer cluster launches secondary enhancers to activate multi-gene locus [RNA-seq]

Project description:Cytokine-sensing primary enhancer cluster launches secondary enhancers to activate multi-gene locus [RNA-seq]

| PRJNA524202 | ENA

Cytokine-sensing primary enhancer cluster launches secondary enhancers to activate multi-gene locus [ChIP-seq]

Project description:Cytokine-sensing primary enhancer cluster launches secondary enhancers to activate multi-gene locus [ChIP-seq]

| PRJNA524204 | ENA

Suppressed cytokine and chemokine transcriptional signatures in mammary stem/progenitor cells are associated with dietary protection against Wnt1-driven mammary tumorigenesis

Project description:Maintenance and propagation of breast cancer stem cells (BCSCs) is mediated via cytokine and growth factor networks. Direct in vivo linkage between dietary regulation of mammary stem (MaSC)/progenitor cell numbers and protection from breast cancer has not been reported. Here, we investigated the effect of post-weaning intake of soy protein isolate (SPI) relative to the control casein (CAS) diet on the stem/progenitor population and tumor formation in MMTV-Wnt1-Transgenic (Wnt1-Tg) female mice. Gene expression profile of the basal (MaSC-enriched) sub-population in preneoplastic Wnt1-Tg mice demonstrated a stem cell-like expression pattern and markedly suppressed expression of inflammatory cytokines, C-X-C family chemokines, and metastasis-associated genes with dietary SPI exposure. four Samples: two CAS diet, two SPI diet

2014-06-30 | E-GEOD-37849 | biostudies-arrayexpress

Lineage-specific and non-specific cytokine-sensing genes respond differentially to the master regulator STAT5

Project description:STAT5, a member of the family of Signal Transducers and Activators of Transcription senses cytokines and controls the biology of cell lineages, including mammary, liver and T cells. Here we show that STAT5 activates lineage-specific and widely expressed genes through different mechanisms. STAT5 preferentially binds to promoter sequences of cytokine-responsive genes expressed across cell types and to putative enhancers of lineage-specific genes. While chromatin accessibility of STAT5-based enhancers was dependent on cytokine exposure, STAT5-responsive promoters of widely expressed target genes were generally constitutively accessible. While the contribution of STAT5 to enhancers is well established, its role on promoters is poorly understood. To address this we focused on Socs2, a widely expressed cytokine-sensing gene. Upon deletion of the STAT5 response elements from the Socs2 promoter, cytokine induction was abrogated, while basal activity remained intact. Our data suggest that promoter-bound STAT5 modulates cytokine responses and enhancer-bound STAT5 is mandatory for gene activation.

2016-12-20 | GSE82275 | GEO

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