About Enhancer

Enhancer ID: E_01_0418
Species: human
Position : chr22:39516355-39518355
Biosample name:
Experiment class : High+Lowthroughput
Enhancer type: Enhancer
Disease: Chronic kidney injury
Pubmed ID:  29887316
Enhancer experiment: Oil red O staining,Western blot,Luciferase assays,quantitative real-time PCR,Histological analysis,Immunofluorescence analysis,Electron microscopy,Laser microdissection,
Enhancer experiment description: ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.

About Target gene

Target gene : --
Strong evidence: qRT-PCR,qPCR,ChIP,3C
Less strong evidence: RNA-Seq
Target gene experiment description: ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.;ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.

About TF

TF name : ATF4EPO
TF experiment: Oil red O staining,Western blot,Luciferase assays,quantitative real-time PCR,Histological analysis,Immunofluorescence analysis,Electron microscopy,Laser microdissection,
TF experiment description: ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.;ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.

About Function

Enhancer function : ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.
Enhancer function experiment: Immunohistochemical staining
Enhancer function
experiment description:
ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
ATF4 Apoptosis signaling pathway panther 104
ATF4 ATF4 activates genes reactome 25
ATF4 ATF6-alpha activates chaperone genes reactome 10
ATF4 Validated transcriptional targets of AP1 family members Fra1 and Fra2 pid 37
ATF4 MAPK signaling pathway kegg 264
ATF4 Protein processing in endoplasmic reticulum kegg 166
ATF4 Long-term potentiation kegg 67
ATF4 Neurotrophin signaling pathway kegg 126
ATF4 GnRH signaling pathway kegg 98
ATF4 Prostate cancer kegg 85
ATF4 Hs_VEGFA-VEGFR2_Signaling_Pathway_WP3888_90000 wikipathways 153
ATF4 Hs_White_fat_cell_differentiation_WP3946_90940 wikipathways 30
ATF4 Hs_One_Carbon_Metabolism_WP241_89671 wikipathways 14
EPO EPO signaling pathway pid 33
EPO EPO signaling pathway(JAK2 STAT1 STAT3 STAT5) ( EPO signaling pathway(JAK2 STAT1 STAT3 STAT5) ) inoh 12
EPO Heterotrimeric GPCR signaling pathway (through G alpha i and pertussis toxin) ( GPCR signaling (pertussis toxin) ) inoh 228
EPO Heterotrimeric GPCR signaling pathway (through G alpha q, PLC beta and ERK cascade) ( GPCR signaling (G alpha q) ) inoh 239
EPO Heterotrimeric GPCR signaling pathway (through G alpha s ACs Epac BRaf and ERKcascade) ( GPCR signaling (G alpha s, Epac and ERK) ) inoh 237
EPO Heterotrimeric GPCR signaling pathway (through_G alpha s_ACs_PKA_BRaf_and_ERKcascade)(canonical) ( GPCR signaling (G alpha s, PKA and ERK) ) inoh 227
EPO Heterotrimeric GTP-binding protein coupled receptor signaling pathway (through G alpha i, adenylate cyclase and cAMP) ( GPCR signaling (G alpha i) ) inoh 228
EPO Heterotrimeric GTP-binding protein coupled receptor signaling pathway (through_G_alpha_s,_cholera_toxin,_adenylate_cyclase_and_cAMP) ( GPCR signaling (cholera toxin) ) inoh 227
EPO HIF-1-alpha transcription factor network pid 67
EPO HIF-2-alpha transcription factor network pid 34
EPO JAK-STAT pathway and regulation pathway ( JAK-STAT pathway and regulation pathway Diagram ) inoh 97
EPO Regulation of gene expression by Hypoxia-inducible Factor reactome 10
EPO Signaling events mediated by Stem cell factor receptor (c-Kit) pid 53
EPO Cytokine-cytokine receptor interaction kegg 213
EPO Hs_MicroRNAs_in_cardiomyocyte_hypertrophy_WP1544_89794 wikipathways 29

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