About Enhancer
| Enhancer ID: | E_02_0920 |
| Species: | mouse |
| Position : | chr8:127047315-127049315   |
| Biosample name: | |
| Experiment class : | Low+High throughput |
| Enhancer type: | Enhancer |
| Disease: | Acute leukemia |
| Pubmed ID: | 24285714 |
| Enhancer experiment: | ChIP,ChIP-seq,Luciferase Reporter Assay,4C,ChIP-qPCR,3C,qPCR |
| Enhancer experiment description: | To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 Mb downstream from Myc that are occupied by SWI/SNF as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably,these distal Myc enhancers coincide with a region that is focally amplified in ~3% of acute myeloid leukemias. |
About Target gene
| Target gene : | MYC(MRTLC,bHLHe39,c-Myc) |
| Strong evidence: | -- |
| Less strong evidence: | ChIP,ChIP-seq,ChIP-qPCR |
| Target gene experiment description: | To explain this observation, we hypothesized that Brg1 regulates Myc transcription in leukemia cells by occupying cell type-specific regulatory elements. We evaluated this possibility by performing chromatin immunoprecipitation (ChIP) followed by next_x0002_generation sequencing (ChIP-seq) analysis of Brg1, his_x0002_tone H3 Lys 4 trimethylation (H3K4me3), and histone H3 Lys 27 acetylation (H3K27ac) in RN2 leukemia cells. |
About TF
| TF name : | SMARCA4(BAF190,BAF190A,BRG1,CSS4,MRD16,RTPS2,SNF2,SNF2L4,SNF2LB,SWI2,hSNF2b)CEBPA(C/EBP-alpha,CEBP)CEBPB(C/EBP-beta,IL6DBP,NF-IL6,TCF5)ERG(erg-3,p55)LMO2(LMO-2,RBTN2,RBTNL1,RHOM2,TTG2) |
| TF experiment: | ChIP-qPCR,shRNA |
| TF experiment description: | Since all of these TFs are expressed in RN2 cells (Supplemental Fig. 13), we anticipated that these factors would occupy E1E5 in leukemia as well. Indeed, we detected occupancy of Lmo2, PU.1, and Erg at various subsets of the E1E5 enhancers in RN2 using ChIP-qPCR (Fig. 5IK). Additionally, we found that the hematopoietic TFs Cebp? and Cebp?, both of which are highly expressed in RN2 cells, also occupied the E1E5 elements (Fig. 5L,M; Supplemental Fig. 13).While expression of several regulators was perturbed upon Brg1 knockdown, Myc was among the most down-regulated genes identified (P < 0.01) (Fig. 3A). Hoxa9, which is a direct target of the MLL-AF9 oncoprotein, was also down-regulated (P < 0.01), albeit to a lesser extent than Myc (Fig. 3A). Gene signatures linked to Myc and Hoxa9 function were globally suppressed following Brg1 knockdown, further confirming an effect on these two pathways (Fig. 3B,C; Supplemental Fig. 5). |
About Function
| Enhancer function : | -- |
| Enhancer function experiment: | -- |
| Enhancer function experiment description: |
-- |
About SNP
| SNP ID: | -- |
Upstream Pathway Annotation of TF
Enhancer associated network
The number on yellow line represents the distance between enhancer and
target gene