ATF4
activating transcription factor 4 | CREB-2, TAXREB67, TXREB

This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]

Developmental clusters: GC3
Biological processes 142 terms
ATF1-ATF4 transcription factor complex (GO:1990590)ATF1-ATF4 transcription factor complex (GO:1990590)ATF1-ATF4 transcription factor complex (GO:1990590)ATF4-CREB1 transcription factor complex (GO:1990589)ATF4-CREB1 transcription factor complex (GO:1990589)ATF4-CREB1 transcription factor complex (GO:1990589)CHOP-ATF4 complex (GO:1990617)CHOP-ATF4 complex (GO:1990617)CHOP-ATF4 complex (GO:1990617)DNA binding (GO:0003677)DNA binding (GO:0003677)DNA binding (GO:0003677)DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228)DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228)DNA-binding transcription factor activity (GO:0003700)DNA-binding transcription factor activity (GO:0003700)DNA-binding transcription factor activity (GO:0003700)DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)DNA-binding transcription factor binding (GO:0140297)HRI-mediated signaling (GO:0140468)Lewy body core (GO:1990037)PERK-mediated unfolded protein response (GO:0036499)PERK-mediated unfolded protein response (GO:0036499)PERK-mediated unfolded protein response (GO:0036499)PERK-mediated unfolded protein response (GO:0036499)RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)RNA polymerase II transcription regulator complex (GO:0090575)RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977)RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629)bone mineralization (GO:0030282)bone mineralization (GO:0030282)cAMP response element binding (GO:0035497)cAMP response element binding protein binding (GO:0008140)cAMP response element binding protein binding (GO:0008140)cellular response to UV (GO:0034644)cellular response to amino acid starvation (GO:0034198)cellular response to amino acid starvation (GO:0034198)cellular response to glucose starvation (GO:0042149)cellular response to hypoxia (GO:0071456)cellular response to leucine starvation (GO:1990253)cellular response to leucine starvation (GO:1990253)cellular response to oxidative stress (GO:0034599)cellular response to oxidative stress (GO:0034599)cellular response to oxidative stress (GO:0034599)centrosome (GO:0005813)centrosome (GO:0005813)chromatin (GO:0000785)circadian regulation of gene expression (GO:0032922)circadian regulation of gene expression (GO:0032922)circadian rhythm (GO:0007623)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytosol (GO:0005829)dendrite membrane (GO:0032590)embryonic hemopoiesis (GO:0035162)embryonic hemopoiesis (GO:0035162)endoplasmic reticulum unfolded protein response (GO:0030968)endoplasmic reticulum unfolded protein response (GO:0030968)gamma-aminobutyric acid signaling pathway (GO:0007214)general transcription initiation factor binding (GO:0140296)gluconeogenesis (GO:0006094)identical protein binding (GO:0042802)integrated stress response signaling (GO:0140467)integrated stress response signaling (GO:0140467)integrated stress response signaling (GO:0140467)intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)lens fiber cell morphogenesis (GO:0070309)lens fiber cell morphogenesis (GO:0070309)leucine zipper domain binding (GO:0043522)mRNA transcription by RNA polymerase II (GO:0042789)mRNA transcription by RNA polymerase II (GO:0042789)negative regulation of cold-induced thermogenesis (GO:0120163)negative regulation of cold-induced thermogenesis (GO:0120163)negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway (GO:1903377)negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway (GO:1903377)negative regulation of potassium ion transport (GO:0043267)negative regulation of transcription by RNA polymerase II (GO:0000122)negative regulation of transcription by RNA polymerase II (GO:0000122)negative regulation of translational initiation in response to stress (GO:0032057)neuron differentiation (GO:0030182)neuron projection (GO:0043005)nuclear periphery (GO:0034399)nuclear speck (GO:0016607)nucleoplasm (GO:0005654)nucleoplasm (GO:0005654)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)plasma membrane (GO:0005886)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of apoptotic process (GO:0043065)positive regulation of gene expression (GO:0010628)positive regulation of gene expression (GO:0010628)positive regulation of neuron apoptotic process (GO:0043525)positive regulation of neuron apoptotic process (GO:0043525)positive regulation of transcription by RNA polymerase I (GO:0045943)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of vascular endothelial growth factor production (GO:0010575)promoter-specific chromatin binding (GO:1990841)promoter-specific chromatin binding (GO:1990841)protein binding (GO:0005515)protein heterodimerization activity (GO:0046982)protein heterodimerization activity (GO:0046982)protein kinase binding (GO:0019901)protein-containing complex (GO:0032991)regulation of DNA-templated transcription (GO:0006355)regulation of DNA-templated transcription (GO:0006355)regulation of apoptotic process (GO:0042981)regulation of osteoblast differentiation (GO:0045667)regulation of osteoblast differentiation (GO:0045667)regulation of synaptic plasticity (GO:0048167)regulation of synaptic plasticity (GO:0048167)regulation of transcription by RNA polymerase II (GO:0006357)regulation of transcription by RNA polymerase II (GO:0006357)response to endoplasmic reticulum stress (GO:0034976)response to endoplasmic reticulum stress (GO:0034976)response to endoplasmic reticulum stress (GO:0034976)response to manganese-induced endoplasmic reticulum stress (GO:1990737)response to nutrient levels (GO:0031667)response to toxic substance (GO:0009636)sequence-specific DNA binding (GO:0043565)sequence-specific double-stranded DNA binding (GO:1990837)transcription by RNA polymerase II (GO:0006366)transcription cis-regulatory region binding (GO:0000976)transcription cis-regulatory region binding (GO:0000976)transcription cis-regulatory region binding (GO:0000976)transcription regulator complex (GO:0005667)
Expression (TPM)
ATF4 — as a Regulated Gene

TFs regulating ATF4 0 TFs

Transcription factors with Perturb-seq knockdown data for ATF4. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = ATF4 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to ATF4

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of ATF4, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr22:39,229,884–39,230,835 290.4 kb Distal (>10kb) Multiome 417
chr22:39,242,211–39,244,345 277.7 kb Distal (>10kb) Multiome 605
chr22:39,310,537–39,311,897 209.4 kb Distal (>10kb) Multiome 655
chr22:39,319,163–39,320,470 200.8 kb Distal (>10kb) Multiome 968
chr22:39,349,608–39,350,646 170.7 kb Distal (>10kb) Multiome 412
chr22:39,388,249–39,388,891 132.1 kb Distal (>10kb) Multiome 336
chr22:39,399,211–39,400,196 120.8 kb Distal (>10kb) Multiome 896
chr22:39,501,766–39,502,757 18.3 kb Distal (>10kb) Multiome 736
chr22:39,519,211–39,521,337 387 bp At TSS Multiome 1150
chr22:39,524,998–39,525,864 4.4 kb Proximal (<10kb) 159
chr22:39,526,604–39,527,231 6.0 kb Proximal (<10kb) 127
chr22:39,528,868–39,529,848 8.8 kb Proximal (<10kb) Multiome 829
chr22:39,532,183–39,533,171 12.3 kb Distal (>10kb) Multiome 799
chr22:39,534,113–39,535,455 14.4 kb Distal (>10kb) Multiome 621
chr22:39,598,010–39,598,521 77.8 kb Distal (>10kb) Multiome 163
chr22:39,661,773–39,663,221 142.0 kb Distal (>10kb) Multiome 260
chr22:39,663,880–39,665,145 144.1 kb Distal (>10kb) Multiome 208
chr22:40,187,442–40,188,012 667.1 kb Distal (>10kb) Multiome HiCAR 86

Genome Browser

Genomic view of the ATF4 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr22:39,219,884 – 40,198,012
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq