Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Runx/CBFβ transcription factor complexes regulate Ccl5 expression through two novel enhancers to enhance tumor immunity [dataset 2]

ABSTRACT: CCL5 (also known as RANTES) was originally known to be important to recruit memory T cells to infected sites, but it received much attention as an inhibitor to HIV’s entry into T lymphocytes of AIDS patients. Recently, it has been reported to be necessary to sustain Trm (Tissue-resident memory) T cells at local tissues as well as to play roles in manipulating tumor microenvironment by both host immunity and cancer cells. Nonetheless, little is known how Ccl5 expression is regulated, thus making it quite difficult for therapeutic intervention. Our study reveals that Runx/CBFβ transcription factor complexes antagonizes Ccl5 expression through two novel transcriptional enhancers. The proximal enhancer is required for the homeostatic expression of Ccl5 during the steady state, meanwhile the distal enhancer is necessary for the expression Ccl5 during the activated stage. We employed enChIP-seq to identify the distal enhancer located 1.35 Mb away from the promoter. This long distance interaction requires the help from Satb1, a global chromatin organizer. Our study reveals that the reduced amounts of Ccl5 by the deletion of the proximal enhancer results in an enhancement of metastasis in B16-F10 melanoma model. On the other hand, a Runx3-mutant mouse line in which Ccl5 expression is increased showed the opposite outcome, suggesting a novel inverse correlation between host Ccl5 levels and metastasis rate.

ORGANISM(S): Mus musculus

PROVIDER: GSE130599 | GEO | 2019/05/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Runx/CBFβ transcription factor complexes regulate Ccl5 expression through two novel enhancers to enhance tumor immunity [dataset 1]

Project description:CCL5 (also known as RANTES) was originally known to be important to recruit memory T cells to infected sites, but it received much attention as an inhibitor to HIV’s entry into T lymphocytes of AIDS patients. Recently, it has been reported to be necessary to sustain Trm (Tissue-resident memory) T cells at local tissues as well as to play roles in manuplating tumor microenvironment by both host immunity and cancer cells. Nonetheless, little is known how Ccl5 expression is regulated, thus making it quite difficult for therapeutic intervention. Our study reveals that Runx/CBFβ transcription factor complexes antagonizes Ccl5 epxression through two novel transcriptional enhancers. The proximal enhancer is required for the homeostatic expression of Ccl5 during the steady state, meanwhile the distal enhancer is necessary for the expression Ccl5 during the activated stage. We employed enChIP-seq to identify the distal enhancer located 1.35 Mb away from the promoter. This long distance interaction requires the help from Satb1, a global chromatin organizer. Our study reveals that the redeced amounts of Ccl5 by the deletion of the proximal enhancer results in an enhancement of metastasis in B16-F10 melanoma model. On the other hand, a Runx3-mutant mouse line in which Ccl5 expression is increased showed the opposite outcome, suggesting a novel inverse correlation between host Ccl5 levels and metastasis rate.

2019-04-25 | GSE130235 | GEO

Runx/CBFβ transcription factor complexes regulate Ccl5 expression through two novel enhancers to enhance tumor immunity [dataset 3]

Project description:CCL5 (also known as RANTES) was originally known to be important to recruit memory T cells to infected sites, but it received much attention as an inhibitor to HIV’s entry into T lymphocytes of AIDS patients. Recently, it has been reported to be necessary to sustain Trm (Tissue-resident memory) T cells at local tissues as well as to play roles in manipulating tumor microenvironment by both host immunity and cancer cells. Nonetheless, little is known how Ccl5 expression is regulated, thus making it quite difficult for therapeutic intervention. Our study reveals that Runx/CBFβ transcription factor complexes antagonizes Ccl5 expression through two novel transcriptional enhancers. The proximal enhancer is required for the homeostatic expression of Ccl5 during the steady state, meanwhile the distal enhancer is necessary for the expression Ccl5 during the activated stage. We employed enChIP-seq to identify the distal enhancer located 1.35 Mb away from the promoter. This long distance interaction requires the help from Satb1, a global chromatin organizer. Our study reveals that the reduced amounts of Ccl5 by the deletion of the proximal enhancer results in an enhancement of metastasis in B16-F10 melanoma model. On the other hand, a Runx3-mutant mouse line in which Ccl5 expression is increased showed the opposite outcome, suggesting a novel inverse correlation between host Ccl5 levels and metastasis rate.

2019-07-12 | GSE134206 | GEO

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation

Project description:Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation

| PRJNA369741 | ENA

Identification of RNAs associated with telomeres by enChIP-RNA-Seq

Project description:Accumulating evidence suggests important roles of RNAs interacting with genomic regions in the regulation of genome functions including X chromosome inactivation and gene expression. However, no method to identify RNAs interacting with a given genomic region in a non-biased manner has been reported. Here, we used engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) combined with the RNA-Seq analysis (enChIP-RNA-Seq) to perform non-biased search of RNAs interacting with telomeres. In enChIP-RNA-Seq, the target genomic regions are captured with an engineered DNA-binding molecule such as a TAL protein. Subsequently, RNAs are purified and subjected to the RNA-Seq analysis. The detected RNAs contained known telomere-binding RNAs including telomerase RNA and Cajal body-specific RNAs. In addition, we detected many novel telomere-binding RNAs. We confirmed binding of candidate RNAs to telomeres by the enChIP-RT-PCR analysis. Identified novel telomere-binding RNAs may play important roles in telomere functions. In addition, our results suggest that enChIP-RNA-Seq analysis would be useful for identification of RNAs interacting with specific genomic regions. RNAs associated with telomeres were identified by using the enChIP technology combined with deep sequencing using Illumina Miseq. Briefly, to isolate telomeres, a TAL protein, Telomere-TAL (Tel-TAL), recognizing a 19-bp sequence containing an array of TTAGGG (telomere repeats) was fused with 3xFLAG tag and NLS (3xFN-Tel-TAL) and LexA protein (3xFNLDD)11 were expressed in a mouse hematopoietic cell line, Ba/F3, respectively. The cells were crosslinked with formaldehyde, and crosslinked chromatin was fragmented by sonication. Subsequently, chromatin complexes containing 3xFN-Tel-TAL or 3xFNLDD were immunoprepicitated with anti-FLAG M2 Ab. Supplementary URL: http://www.nature.com/srep/2013/131108/srep03171/full/srep03171.html

2015-04-16 | E-GEOD-60425 | biostudies-arrayexpress

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation IV

Project description:Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation IV

| PRJNA610600 | ENA

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation III

Project description:Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation III

| PRJNA610601 | ENA

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation I

Project description:Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation I

| PRJNA610603 | ENA

Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation II

Project description:Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation II

| PRJNA610602 | ENA

Transcription factor trapping by RNA in gene regulatory elements (GRO-Seq)

Project description:Transcription factors (TFs) bind specific sequences in promoter-proximal and distal DNA elements in order to regulate gene transcription. RNA is transcribed from both promoter-proximal and distal DNA elements, and some DNA-binding TFs have also been shown to bind RNA. These obsevations led us to postulate that RNA transcribed from regulatory elements contributes to stable TF occupancy at these regulatory elements. We show here that the ubiquitously expressed TF YY1 binds to both proximal and distal regulatory elements and to the RNA species associated with these elements near active genes in embryonic stem cells. Inhibition of transcription from these elements reduces YY1 occupancy. In contrast, tethering of RNA species near YY1 DNA binding sites enhances YY1 occupancy. We propose that RNA acts as trap to maintain certain TFs at active enhancer and promoter-proximal regulatory elements. Thus, transcriptional control generally involves a positive feedback loop, where YY1 and other TFs stimulate local transcription, and newly transcribed nascent RNA reinforces local TF occupancy. This model helps explain why TFs occupy only the small fraction of their consensus motifs in the mammalian genome where transcription is detected. GRO-Seq in mouse embryonic stem cells treated with transcription-altering drugs

2015-10-29 | E-GEOD-68197 | biostudies-arrayexpress

Transcription factor trapping by RNA in gene regulatory elements (CLIP-Seq)

2015-10-29 | E-GEOD-68196 | biostudies-arrayexpress