About Enhancer
| Enhancer ID: | E_01_234 | |
| Enhancer symbol: | -- | |
| Species: | Human | |
| Position : | chr4:26075179-26135897   |
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| Biosample name: | CD4+ T Cell | |
| Experiment class : | Low+High throughput |
| Enhancer type: | Enhancer | |
| Disease: | Rheumatoid Arthritis | |
| DO: | DOID:7148 | |
| Mesh: | D001172 | |
| Distance from TSS: | >2KB | |
| Pubmed ID: | 26604133 |
| Enhancer experiment: | ChIP-seq,PCR,ELISA,qPCR | |
| Enhancer experiment description: | Genome-wide association studies of rheumatoid arthritis (RA) identified a susceptibility locus, rs874040CC, which implicated the RBPJ gene. Here, chromatin state mapping generated using the chromHMM algorithm reveals strong enhancer regions containing DNase I hypersensitive sites overlapping the rs874040 linkage disequilibrium block in human memory, but not in naïve CD4+ T cells. The rs874040 overlapping this chromatin state was associated with increased RBPJ expression in stimulated memory CD4+ T cells from healthy subjects homozygous for the risk allele (CC) compared with memory CD4+ T cells bearing the protective allele (GG). In order to understand whether rs874040 allele status can impact gene regulation,we utilized chromatin states annotation of the human reference genome predicted using the chromHMM algorithm (26) with 15-state model parameters that are provided by the NIH Roadmap Epigenomics Consortium in public domain (27).Our analysis reveals (i) enhancer regions containing DNase I hypersensitive sites, and (ii)weak transcriptio nmarks within the rs874040 LD block and upstream of the RBPJ transcription start site (TSS) in memory but not in naïve T cells (Fig. 1A and B). We found that healthy donors homozygous for the rs874040CC risk allele have increased RBPJ mRNA expression (P = 0.0017) in CD4+ CD45RO+ memory T cells (Fig. 2C). This was confirmed at the protein level by ELISA, showing significant elevated RBPJ expression in CD4+ CD45RO+ memory T cells (P =0.04) (Fig. 2D). All RBPJ transcripts contain a putative nuclear localization signal, an important component of RBPJ nuclear translocation to activate target gene transcription (32).Therefore,we carried out an isoform specific quantitative PCR (qPCR) assay in TCR-stimulated memory T cells. We found a rapid increase in Isoform2 (NM_015874) (P = 0.042), Isoform3 (NM_202283) (P = 0.0083)and Isoform 4 (NM_202284) (P =8.29×10−09 )3h after stimulation of memory T cells from subjects with the rs874040CC risk allele, whilethe expression of Isoform 1 (NM_005349) was unchanged (Supple-mentary Material, Fig. S1B). |
About Target gene
| Target gene : | RBPJ(AOS3,CBF1,IGKJRB,IGKJRB1,KBF2,RBP-JK,RBPSUH,SUH,csl,RBPJ) | |
| Strong evidence: | -- | |
| Less strong evidence: | PCR,ELISA,qPCR | |
| Target gene experiment description: | In order to understand whether rs874040 allele status can impact gene regulation,we utilized chromatin states annotation of the human reference genome predicted using the chromHMM algorithm (26) with 15-state model parameters that are provided by the NIH Roadmap Epigenomics Consortium in public domain (27).Our analysis reveals (i) enhancer regions containing DNase I hypersensitive sites, and (ii)weak transcriptio nmarks within the rs874040 LD block and upstream of the RBPJ transcription start site (TSS) in memory but not in naïve T cells (Fig. 1A and B). We found that healthy donors homozygous for the rs874040CC risk allele have increased RBPJ mRNA expression (P = 0.0017) in CD4+ CD45RO+ memory T cells (Fig. 2C). This was confirmed at the protein level by ELISA, showing significant elevated RBPJ expression in CD4+ CD45RO+ memory T cells (P =0.04) (Fig. 2D). All RBPJ transcripts contain a putative nuclear localization signal, an important component of RBPJ nuclear translocation to activate target gene transcription (32).Therefore,we carried out an isoform specific quantitative PCR (qPCR) assay in TCR-stimulated memory T cells. We found a rapid increase in Isoform2 (NM_015874) (P = 0.042), Isoform3 (NM_202283) (P = 0.0083)and Isoform 4 (NM_202284) (P =8.29×10−09 )3h after stimulation of memory T cells from subjects with the rs874040CC risk allele, whilethe expression of Isoform 1 (NM_005349) was unchanged (Supple-mentary Material, Fig. S1B). |
About TF
| TF name : | -- | |
| TF experiment: | -- | |
| TF experiment description: | -- |
About Function
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
-- |
About SNP
| SNP experiment: | ChIP,PCR |
Enhancer associated network
The number on yellow line represents the distance between enhancer and target gene
