Enhancer type: | Enhancer | |
Disease: | Leukemia | |
DO: | DOID:1240 | |
Mesh: | D007938 | |
Distance from TSS: | >2KB | |
Pubmed ID: | 25185713 |
Enhancer experiment: | ChIP,3C,Transgenic mice | |
Enhancer experiment description: | Mechanistically, by using a knockin mouse model in which all three Runx binding sites in the214kb enhancer of PU.1 are disrupted, we observed failure to form chromosomal interactions between the PU.1 enhancer and its proximal promoter. Consequently, decreased PU.1 levels resulted in diminished long-term HSC function through HSC exhaustion, which could be rescued by reintroducing a PU.1 transgene. |
Target gene : | Spi1(OF,PU.1,SFPI1,SPI-1,SPI-A) | |
Strong evidence: | 3C | |
Less strong evidence: | RT-PCR,PCR,Transgenic mice | |
Target gene experiment description: | Mechanistically, by using a knockin mouse model in which all three Runx binding sites in the 214kb Enhancer of PU.1 are disrupted, we observed failure to form chromosomal interactions between the PU.1 Enhancer and its proximal promoter.Runx-dependent PU.1 chromatin interaction and transcription of PU.1 are essential for both normal and leukemia stem cells. |
TF name : | Runx1(AML1,AML1-EVI-1,AMLCR1,CBF2alpha,CBFA2,EVI-1,PEBP2aB,PEBP2alpha)Runx2(AML3,Cbf,Cbfa-1,Cbfa1,LS3,Osf2,PEBP2aA,Pebp2a1,Pebpa2a)Runx3(AML2,CBFA3,PEBP2aC) | |
TF experiment: | ChIP | |
TF experiment description: | ChIP analyses of total bone marrow cells con?rmed the loss of Runx binding to the 214kb URE in PU.1-URE-mRunx mice (supplemental Figure 1C). Importantly, PU.1 mRNA levels in HSCs of PU.1-URE-mRunxmicewere reduced by 72%in comparisonwith controls (WT), greater than the average reduction of 63% observed in Runx1 knockout mice (Figure 1D). These results revealed the major role of the URE Runx sites for PU.1 transcription in HSCs. |
Enhancer function : | -- |
Enhancer function experiment: | -- |
Enhancer function experiment description: |
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SNP ID: | -- | |
SNP position: | -- |
SNP experiment: | -- |
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