About Enhancer
| Enhancer ID: | E_02_0806 |
| Species: | human |
| Position : | chr11:8240851-8242851   |
| Biosample name: | |
| Experiment class : | Low+High throughput |
| Enhancer type: | Enhancer |
| Disease: | -- |
| Pubmed ID: | 28260788 |
| Enhancer experiment: | ChIP-seq,Luciferase Reporter Assay,ChIA-PET |
| Enhancer experiment description: | To identify mutations in the T-ALL genome that might signi?cantly alter oncogene expression, we focused our search on aberrant,sample-speci?c enhancers in 10 different human T-ALL cell lines as identi?ed by H3K27ac ChIP-seq. The aberrant active enhancer we identi?ed was present upstream of the LMO1 gene in RPMI-8402 and Jurkat T-ALL cell lines. To ascertain whether this single base-pair substitution can activate LMO1 gene expression, we cloned a 585-bp genomic DNA fragment from either the C allele or T allele upstream of luciferase and tested the enhancer activity of this fragment in a reporter assay.When introduced into Jurkat cells, the construct containing the T allele exhibited robust reporter activity, which was four-fold greater than that of the fragment containing the C allele (Figure 3f).Taken together, we have shown that the somatically acquired C-to-T mutation that creates a MYB binding motif ~ 4 kb upstream of the proximal transcription start site of LMO1 in T-ALL can generate an active transcriptional enhancer that drives monoallelic overexpression of the LMO1 oncogene. We also used chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) 24 in Jurkat cells to demonstrate that the stream of the proximal LMO1 transcription start site used by Jurkat cells (Figure 5d and Supplementary Figure S1), indicating that the active enhancer mediated by the acquired MYB binding motif loops to the LMO1 gene promoter region to regulate the transcription of LMO1 (Figure 5e). |
About Target gene
| Target gene : | LMO1(RBTN1,RHOM1,TTG1) |
| Strong evidence: | -- |
| Less strong evidence: | Luciferase Reporter Assay |
| Target gene experiment description: | To ascertain whether this single base-pair substitution can activate LMO1 gene expression, we cloned a 585-bp genomic DNA fragment from either the C allele or T allele upstream of luciferase and tested the enhancer activity of this fragment in a reporter assay.When introduced into Jurkat cells, the construct containing the T allele exhibited robust reporter activity, which was four-fold greater than that of the fragment containing the C allele (Figure 3f).Taken together, we have shown that the somatically acquired C-to-T mutation that creates a MYB binding motif ~ 4 kb upstream of the proximal transcription start site of LMO1 in T-ALL can generate an active transcriptional enhancer that drives monoallelic overexpression of the LMO1 oncogene. |
About TF
| TF name : | MYB(Cmyb,c-myb,c-myb_CDS,efg) |
| TF experiment: | ChIP-seq |
| TF experiment description: | Analysis of the genomic sequences of both C and T alleles, using UniPROBE and HOCOMOCO databases, identi?ed a de novo-binding motif for the MYB transcription factor (Figure 3a and Supplementary Table S3), while analysis of the MYB and H3K27ac ChIP-seq DNA sequence reads aligned with this site demon-strated that MYB and H3K27ac were bound almost exclusively by the T allele (Figure 3b).Knockdown of MYB expression using lentivirus-transduced shRNA decreased the expression of LMO1 signi?cantly in Jurkat cells (Figure 3d), indicating that MYB binding to the somatically acquired heterozygous MYB binding motif leads to enhanced expression of LMO1 in T-ALL from the same allele. |
About Function
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
-- |
About SNP
| SNP ID: | -- |
Upstream Pathway Annotation of TF
| GeneName | Pathway Name | Source | Gene Number |
|---|---|---|---|
| MYB | AP-1 transcription factor network | pid | 71 |
| MYB | C-MYB transcription factor network | pid | 87 |
| MYB | Factors involved in megakaryocyte development and platelet production | reactome | 111 |
| MYB | IL2 signaling events mediated by PI3K | pid | 38 |
| MYB | IL4-mediated signaling events | pid | 66 |
| MYB | Notch-mediated HES/HEY network | pid | 48 |
| MYB | Prolactin | netpath | 105 |
| MYB | Hs_Neural_Crest_Differentiation_WP2064_79263 | wikipathways | 40 |
Enhancer associated network
The number on yellow line represents the distance between enhancer and
target gene