Alternative titles; symbols
Other entities represented in this entry:
HGNC Approved Gene Symbol: FEV
Cytogenetic location: 2q35 Genomic coordinates (GRCh38): 2:218,981,087-218,985,184 (from NCBI)
FEV belongs to a family of ETS transcription factors (see 164720) defined by the presence of a highly conserved 85-amino acid ETS domain. The ETS domain mediates specific binding to purine-rich DNA sequences characterized by an invariant GGA/TA core element (Peter et al., 1997).
By RT-PCR, Peter et al. (1997) cloned FEV from several neuroblastoma samples and Ewing sarcoma (ES; 612219) tumor cell lines. They also screened a Ewing-specific cDNA library using the PCR product as probe. The deduced 238-amino acid protein contains a short N-terminal domain followed by an ETS DNA-binding domain that is most closely related to that of FLI1 (193067). The C terminus of FEV contains a 112-amino acid domain rich in ala, pro, leu, and gly, including a continuous stretch of 12 alanines characteristic of transcription repressors. Northern blot analysis revealed expression of a 1.9-kb transcript in adult prostate and small intestine, but no expression was detected in other adult or fetal tissues examined.
Fyodorov et al. (1998) cloned rat FEV, which they designated PET1. Northern blot analysis and in situ hybridization detected expression in adrenal medulla, brain, intestine, and eye.
Fyodorov et al. (1998) determined that rat PET1 bound specifically to an oligonucleotide containing a single polyomavirus enhancer activator-3 (PEA3) ETS domain-binding site. Cotransfection of PET1 with a reporter plasmid containing this motif resulted in dose-dependent repression of reporter activity. PET1 also activated reporter activity through an enhancer found within the 3-prime untranslated region of the beta-4 subunit of the acetylcholine receptor (118509). Fyodorov et al. (1998) concluded that rat PET1 is a transcriptional regulator of genes involved in cholinergic neurotransmission.
Hendricks et al. (2003) found that proper development of the entire central 5-hydroxytryptamine (5-HT) system was disrupted in Pet1-null mice. Most 5-HT neurons failed to differentiate in null mice, and remaining 5-HT neurons showed deficient expression of genes required for 5-HT synthesis, uptake, and storage. No effect on other monoamine systems was evident. Adult null mice showed heightened anxiety-like and aggressive behavior. The authors suggested that Pet1 is a critical determinant of 5-HT neuron identity and may play a role in serotonergic modulation of behavior.
Peter et al. (1997) determined that the FEV gene contains 3 exons.
By somatic cell hybrid analysis, Peter et al. (1997) mapped the FEV gene to chromosome 2.
Peter et al. (1997) described a t(2;22) translocation that fused the N-terminal transcription-activation domain of EWS (133450) to the ETS DNA-binding domain of FEV in a paraspinal tumor in a 2-year-old girl and in an extraosseous maxillary tumor in a 15-year-old boy. Sequence analysis indicated that exon 10 of EWS was linked in-frame to FEV.
To examine putative central and peripheral sources of embryonic brain 5-HT (serotonin), Bonnin et al. (2011) used Pet1-null mice in which most dorsal raphe neurons lack 5-HT. They detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, Bonnin et al. (2011) investigated the nature of this exogenous source and uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. Mouse placenta expresses both Tph1 (191060) and Aadc (608643) in the syncytiotrophoblastic cell layer at embryonic days 10.5 through 14.5. Human placental fetal villi at 11 weeks' gestation showed robust 5-HT neosynthesis, indicating that a placental source of 5-HT is important for human fetal development. Bonnin et al. (2011) concluded that their study revealed a new, direct role for placental metabolic pathways in modulating fetal brain development and indicated that maternal-placental-fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.
Bonnin, A., Goeden, N., Chen, K., Wilson, M. L., King, J., Shih, J. C., Blakely, R. D., Deneris, E. S., Levitt, P. A transient placental source of serotonin for the fetal forebrain. Nature 472: 347-350, 2011. [PubMed: 21512572] [Full Text: https://doi.org/10.1038/nature09972]
Fyodorov, D., Nelson, T., Deneris, E. Pet-1, a novel ETS domain factor that can activate neuronal nAchR gene transcription. J. Neurobiol. 34: 151-163, 1998. [PubMed: 9468386]
Hendricks, T. J., Fyodorov, D. V., Wegman, L. J., Lelutiu, N. B., Pehek, E. A., Yamamoto, B., Silver, J., Weeber, E. J., Sweatt, J. D., Deneris, E. S. Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior. Neuron 37: 233-247, 2003. [PubMed: 12546819] [Full Text: https://doi.org/10.1016/s0896-6273(02)01167-4]
Peter, M., Couturier, J., Pacquement, H., Michon, J., Thomas, G., Magdelenat, H., Delattre, O. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene 14: 1159-1164, 1997. [PubMed: 9121764] [Full Text: https://doi.org/10.1038/sj.onc.1200933]