ATF7
Plays important functions in early cell signaling. Binds the cAMP response element (CRE) (consensus: 5-GTGACGT[AG][AG]-3), a sequence present in many viral and cellular promoters. Activator of the NF-ELAM1/delta-A site of the E-selectin promoter. Has no intrinsic transcriptional activity, but activates transcription on formation of JUN or FOS heterodimers. Also can bind TRE promoter sequences when heterodimerized with members of the JUN family.
Full Name
Activating Transcription Factor 7
Function
Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation (PubMed:29490055).
In absence of stress, contributes to the formation of heterochromatin and heterochromatin-like structure by recruiting histone H3K9 tri- and di-methyltransferases thus silencing the transcription of target genes such as STAT1 in adipocytes, or genes involved in innate immunity in macrophages and adipocytes (By similarity).
Stress induces ATF7 phosphorylation that disrupts interactions with histone methyltransferase and enhances the association with coactivators containing histone acetyltransferase and/or histone demethylase, leading to disruption of the heterochromatin-like structure and subsequently transcriptional activation (By similarity).
In response to TNF-alpha, which is induced by various stresses, phosphorylated ATF7 and telomerase are released from telomeres leading to telomere shortening (PubMed:29490055).
Plays also a role in maintaining epithelial regenerative capacity and protecting against cell death during intestinal epithelial damage and repair (By similarity).
Isoform 4: Acts as a dominant repressor of the E-selectin/NF-ELAM1/delta-A promoter.
Isoform 5: Acts as a negative regulator, inhibiting both ATF2 and ATF7 transcriptional activities. It may exert these effects by sequestrating in the cytoplasm the Thr-53 phosphorylating kinase, preventing activation.
Biological Process
Negative regulation of transcription by RNA polymerase II Source: NTNU_SB
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Viral process Source: UniProtKB-KW
Cellular Location
Nucleus; Nucleoplasm; Telomere. Mainly nucleoplasmic. Restricted distribution to the perinuculear region. The sumoylated form locates to the nuclear periphery.
Isoform 5: Cytoplasm
PTM
On EGF stimulation, phosphorylated first on Thr-53 allowing subsequent phosphorylation on Thr-51. This latter phosphorylation prevents sumoylation, increases binding to TAF12 and enhances transcriptional activity.
Sumoylation delays nuclear localization and inhibits transactivation activity through preventing binding to TAF12. RANBP2 appears to be the specific E3 ligase.
On EGF stimulation, phosphorylated first on Thr-53 allowing subsequent phosphorylation on Thr-51. This latter phosphorylation prevents sumoylation, increases binding to TAF12 and enhances transcriptional activity (PubMed:18950637). Social isolation stress as well as TNF-alpha also induce the phosphorylation of ATF7 (PubMed:29490055). Phosphorylated in proliferating colonic and small intestinal epithelial cells (By similarity).