About Enhancer

Enhancer ID: E_01_010
Enhancer symbol: --
Species: Human
Position : chr8:23422136-23432636
Biosample name: Human CD34+ Hematopoietic Stem/Progenitor Cell
Experiment class : Low+High throughput
Enhancer type: Enhancer
Disease: --
DO: --
Mesh: --
Distance from TSS: >2KB
Pubmed ID:  26766440
Enhancer experiment: CRISPR/Cas9,ChIP-seq
Enhancer experiment description: The enhancer cluster upstream of the SLC25A37 gene, consisting of three distinct constituent enhancers as measured by H3K4me1 and H3K27ac ChIP-seq, is defined as an erythroid-specific super-enhancer in both human (A5 ProE) and mouse (G1ER) erythroid cells (Figure 3A; Table S4). To define the regulatory components of the SLC25A37 super-enhancer, we asked whether the function of each constituent enhancer depends on the activity of neighboring enhancers in situ. We employed site-directed loss-of-function analysis of the SLC25A37 super-enhancer constituents using CRISPR/Cas9-mediated genomic engineering.We focused on the orthologous mouse super-enhancer in the murine G1E/G1ER erythroid cell model (Welch et al., 2004). We designed sequence-specific guide RNAs (or sgRNAs) flanking each constituent enhancer (E1, E2 and E3) or the promoter (P) (Figure 3B). Upon transfection into undifferentiated G1E cells together with an SpCas9 expressing construct, we screened and obtained multiple independent single cell-derived clones containing bi-allelic deletion of each enhancer (Figure S2B,C). Surprisingly, knockout of individual enhancers confer markedly varying effects on Slc25a37 expression. Specifically, while deletion of E1 or E2 individually only modestly or slightly impairs Slc25a37 activation during differentiation, respectively, E3 deletion abolishes its activation resulting in a 15-fold decrease in expression (48h after β-estradiol treatment; Figure 3C).

About Target gene

Target gene : SLC25A37 (HT015,MFRN,MFRN1,MSC,MSCP,PRO1278,PRO1584,PRO2217)
Strong evidence: CRISPR/Cas9
Less strong evidence: ChIP-seq
Target gene experiment description: The enhancer cluster upstream of the SLC25A37 gene, consisting of three distinct constituent enhancers as measured by H3K4me1 and H3K27ac ChIP-seq, is defined as an erythroid-specific super-enhancer in both human (A5 ProE) and mouse (G1ER) erythroid cells (Figure 3A; Table S4). To define the regulatory components of the SLC25A37 super-enhancer, we asked whether the function of each constituent enhancer depends on the activity of neighboring enhancers in situ. We employed site-directed loss-of-function analysis of the SLC25A37 super-enhancer constituents using CRISPR/Cas9-mediated genomic engineering.We focused on the orthologous mouse super-enhancer in the murine G1E/G1ER erythroid cell model (Welch et al., 2004). Surprisingly, knockout of individual enhancers confer markedly varying effects on Slc25a37 expression. Specifically, while deletion of E1 or E2 individually only modestly or slightly impairs Slc25a37 activation during differentiation, respectively, E3 deletion abolishes its activation resulting in a 15-fold decrease in expression (48h after β-estradiol treatment; Figure 3C).

About TF

TF name : GATA1(ERYF1,GATA-1,GF-1,GF1,NF-E1,NFE1,XLANP,XLTDA,XLTT)TAL1(SCL,TCL5,bHLHa17,tal-1)
TF experiment: ChIP-seq
TF experiment description: Strikingly, while only 3% (22,570 of 707,718) of the GATA1 motif-matched loci are covered by GATA1 ChIP-seq at a genome scale in ProEs, 34% of identified GATA1 motifs are covered by GATA1 within the Enhancer context.Similar pattern is observed for another principal erythroid regulator TAL1.

About Function

Enhancer function : GATA2-to-GATA1 switch is prevalent at dynamic enhancers and drives erythroid enhancer commissioning.
Enhancer function experiment: CRISPR/Cas9
Enhancer function
experiment description:
While the E2 and E3 Enhancers are indispensable for maximal Gata2 activation in stem/progenitor cells, the E1 Enhancer is required to maintain Gata2 repression in committed erythroid cells.

About SNP

SNP ID: --
SNP position: --
SNP experiment: --

Enhancer associated network

The number on yellow line represents the distance between enhancer and target gene

Expression of target genes for the enhancer


Enhancer associated SNPs