E2F7

E2F7
Identifikatori
Aliasi	E2F7
Vanjski ID-jevi	OMIM: 612046 MGI: 1289147 HomoloGene: 18685 GeneCards: E2F7
Lokacija gena (čovjek)
Hrom.	Hromosom 12 (čovjek)
Kraj	77,065,569 bp
Lokacija gena (miš)
Hrom.	Hromosom 10 (miš)
Kraj	110,623,245 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vezivanje sa DNK; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • GO:0001106 transcription corepressor activity; • GO:0001948, GO:0016582 vezivanje za proteine; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • vezivanje identičnih proteina; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001158 cis-regulatory region sequence-specific DNA binding; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • transcription factor binding; • sequence-specific DNA binding;
Ćelijska komponenta	• transcription regulator complex; • jedro; • nukleoplazma; • nuclear speck; • RNA polymerase II transcription regulator complex;
Biološki proces	• trophoblast giant cell differentiation; • GO:0009373 regulation of transcription, DNA-templated; • chorionic trophoblast cell differentiation; • negative regulation of transcription involved in G1/S transition of mitotic cell cycle; • Placentacija; • DNA damage response, signal transduction by p53 class mediator; • hepatocyte differentiation; • GO:1901227 negative regulation of transcription by RNA polymerase II; • transcription, DNA-templated; • cellular response to DNA damage stimulus; • GO:1990376 negative regulation of G1/S transition of mitotic cell cycle; • ćelijski ciklus; • negative regulation of cytokinesis; • positive regulation of DNA endoreduplication; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • sprouting angiogenesis; • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; • negative regulation of cell population proliferation; • regulation of cell cycle;
	Izvori:Amigo / QuickGO
Ortolozi
	144455
	52679
	ENSG00000165891
	ENSMUSG00000020185
	Q96AV8
	Q6S7F2
	NM_203394
	NM_178609; NM_001358560
	NP_976328
	NP_848724; NP_001345489
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Transkripcijski faktor E2F7 je protein koji je kod ljudi kodiran genom E2F7.^[5]^[6] Faktori transkripcije E2F, poput E2F7, imaju bitnu ulogu u regulaciji progresije ćelijskog ciklusa (Di Stefano et al., 2003).

Di Stefano et al (2003) utvrdili su da gen E2F7 sadrži 13 egzona, od kojih je prvi nekodirajući. Promotorska regija sadrži četiri potencijalna mjesta vezanja za E2F.^[7]

Analizom sekvence i analizom BAC klonova, de Bruin et al. (2003) mapirali su ljudske i mišje gene E2F7 u hromosome 12, odnosno 10.^[8]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 911 aminokiselina, a molekulska težina 99.888 Da.^[9]

10	20	30	40	50
MEVNCLTLKD	LISPRQPRLD	FAVEDGENAQ	KENIFVDRSR	MAPKTPIKNE
PIDLSKQKKF	TPERNPITPV	KFVDRQQAEP	WTPTANLKML	ISAASPDIRD
REKKKGLFRP	IENKDDAFTD	SLQLDVVGDS	AVDEFEKQRP	SRKQKSLGLL
CQKFLARYPS	YPLSTEKTTI	SLDEVAVSLG	VERRRIYDIV	NVLESLHLVS
RVAKNQYGWH	GRHSLPKTLR	NLQRLGEEQK	YEEQMAYLQQ	KELDLIDYKF
GERKKDGDPD	SQEQQLLDFS	EPDCPSSSAN	SRKDKSLRIM	SQKFVMLFLV
SKTKIVTLDV	AAKILIEESQ	DAPDHSKFKT	KVRRLYDIAN	VLTSLALIKK
VHVTEERGRK	PAFKWIGPVD	FSSSDEELVD	VSASVLPELK	RETYGQIQVC
AKQKLARHGS	FNTVQASERI	QRKVNSEPSS	PYREEQGSGG	YSLEIGSLAA
VYRQKIEDNS	QGKAFASKRV	VPPSSSLDPV	APFPVLSVDP	EYCVNPLAHP
VFSVAQTDLQ	AFSMQNGLNG	QVDVSLASAA	SAVESLKPAL	LAGQPLVYVP
SASLFMLYGS	LQEGPASGSG	SERDDRSSEA	PATVELSSAP	SAQKRLCEER
KPQEEDEPAT	KRQSREYEDG	PLSLVMPKKP	SDSTDLASPK	TMGNRASIPL
KDIHVNGQLP	AAEEISGKAT	ANSLVSSEWG	NPSRNTDVEK	PSKENESTKE
PSLLQYLCVQ	SPAGLNGFNV	LLSGSQTPPT	VGPSSGQLPS	FSVPCMVLPS
PPLGPFPVLY	SPAMPGPVSS	TLGALPNTGP	VNFSLPGLGS	IAQLLVGPTA
VVNPKSSTLP	SADPQLQSQP	SLNLSPVMSR	SHSVVQQPES	PVYVGHPVSV
VKLHQSPVPV	TPKSIQRTHR	ETFFKTPGSL	GDPVLKRRER	NQSRNTSSAQ
RRLEIPSGGA	D

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Kloniranje i ekspresija

Skriningom ljudskih fibroblasta na gene regulisane E2F1, nakon čega je uslijedila analiza baze podataka i RT-PCR biblioteke cDNK fibroblasta, Di Stefano et al. (2003) klonirali su 2 varijante prerade E2F7 koje su označili kao E2F7A i E2F7B. E2F7A nedostaje egzon 12 i kodira protein od 728 aminokiselina, dok E2F7B uključuje egzon 12 i kodira protein sa 911 aminokiselina. Proteini E2F7A i E2F7B razlikuju se u sekvenci, tek nakon aminokiseline 713, a oba imaju po dva domena za vezivanje DNK tipa E2F, tipa N koje sadrže visoko konzervirane ostatke uključene u vezivanje. Obje izoforme bile su eksprimirane u svim ispitivanim ćelijskim linijama, pri čemu je E2F7B najzastupljeniji.

De Bruin et al. (2003) identificirali su mišji E2f7, koji kodira zaključeni protein od 904 aminokiseline. Otkrivena Northern blot analiza pokazala je najveću ekspresiju E2f7 u mišjoj koži i timusu, s malo ili bez ekspresije u mozgu, mišićima ili želucu. E2f7 označen epitopom lokaliziran u jedru mišjih embrionskih fibroblasta, bez obzira na stanje ćelijskog ciklusa.

Funkcija gena

Koristeći kvantitativnu RT-PCR analizu, Di Stefano et al. (2003) otkrili su da je aktivacija E2F1 rezultirala šest puta povećanim nivoom iRNK E2F7 u ljudskim fibroblastima. E2F1 i, u manjoj mjeri, E2F4 zauzimali su promotor E2F7 u ćelijama ljudskog osteosarkoma U2OS. Ektopska ekspresija E2F7 u ćelijama U2OS potisnula je ciljne gene E2F i dovela do nakupljanja ćelija u G1 fazi ciklusa. E2F7 povezan je s promotorima reguliranim E2F in vivo, a povezanost se povećala u S fazi. Analiza mutacija otkrila je da su za vezivanje DNK potrebna oba domena E2F7 . Testovi imunoprecipitacije hromatina (ChIP) pokazali su da su za vezivanje DNK E2F7 veže promotore podskupa gena ovisnih o E2F, uključujući E2F1 i CDC6 (CDC18L, u ćelijama U2OS i ljudskim fibroblastima. Inhibicija ekspresije E2F7 rezultirala je specifičnom derepresijom promotora E2F1 i CDC6. Zaključili su da je E2F7 jedinstveni represor podskupa E2F ciljnih gena čiji su proizvodi potrebni za napredovanje ćelijskog ciklusa.

De Bruin et al. (2003) otkrili su da stimulacija seruma povećava ekspresiju E2f7 u embrionskim fibroblastima miša u mirovanju. Prekomjerna ekspresija E2f7 rezultirala je nakupljanjem ćelija u G2/M i smanjenjem ćelija u G1-fazi.

Životinjski model

Li et al. (2008) otkrili su da su se i miševi E2f7 –/– i E2f8 –/– miševi normalno razvijali i doživjeli starost. Ukrštanjem su proizvedeni miševi E2f7 +/– E2f8 –/– koji su bili razvojno normalni, ali većina životinja E2f7 –/– E2f8 +/– uginula je u prva tri mjeseca života. Embrioni s dvostrukim izbacivanjem uginuli su do embrionskog dana 11,5, zbog masovne apoptoze i širenja krvnih sudova i pokazali su povećanu ekspresiju E2f1 i p53 (TP53), kao i mnoge gene povezane sa stresom. ChIP analiza pokazala je homo– i heterodimere E2f7 i E2f8 na ciljnim promotorima, uključujući E2f1 i Cdc6. Gubitak E2f1 ili p53 potisnuo je masovnu apoptozu u embrionima s dvostrukim nokautom.^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000165891 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020185 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ de Bruin A, Maiti B, Jakoi L, Timmers C, Buerki R, Leone G (Oct 2003). "Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation". J Biol Chem. 278 (43): 42041–9. doi:10.1074/jbc.M308105200. PMID 12893818.
^ "Entrez Gene: E2F7 E2F transcription factor 7".
^ Di Stefano, L., Jensen, M. R., Helin, K. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes. EMBO J. 22: 6289-6298, 2003. PubMed: 14633988
^ de Bruin, A., Maiti, B., Jakoi, L., Timmers, C., Buerki, R., Leone, G. Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation. J. Biol. Chem. 278: 42041-42049, 2003. PubMed: 12893818
^ "UniProt, Q96AV8". Pristupljeno 7. 8. 2021.
^ Li, J., Ran, C., Li, E., Gordon, F., Comstock, G., Siddiqui, H., Cleghorn, W., Chen, H.-Z., Kornacker, K., Liu, C.-G., Pandit, S. K., Khanizadeh, M., Weinstein, M., Leone, G., de Bruin, A. Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Dev. Cell 14: 62-75, 2008. PubMed: 18194653

Dopunska literatura

Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
Reimer D, Sadr S, Wiedemair A, et al. (2007). "Clinical relevance of E2F family members in ovarian cancer--an evaluation in a training set of 77 patients". Clin. Cancer Res. 13 (1): 144–51. doi:10.1158/1078-0432.CCR-06-0780. PMID 17200349.
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Logan N, Graham A, Zhao X, et al. (2005). "E2F-8: an E2F family member with a similar organization of DNA-binding domains to E2F-7". Oncogene. 24 (31): 5000–4. doi:10.1038/sj.onc.1208703. PMID 15897886.
Logan N, Delavaine L, Graham A, et al. (2004). "E2F-7: a distinctive E2F family member with an unusual organization of DNA-binding domains". Oncogene. 23 (30): 5138–50. doi:10.1038/sj.onc.1207649. PMID 15133492.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Di Stefano L, Jensen MR, Helin K (2004). "E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes". EMBO J. 22 (23): 6289–98. doi:10.1093/emboj/cdg613. PMC 291854. PMID 14633988.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000165891 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020185 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid12893818-5] Bruin A, Maiti B, Jakoi L, Timmers C, Buerki R, Leone G (Oct 2003). "Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation". J Biol Chem. 278 (43): 42041–9. doi:10.1074/jbc.M308105200. PMID 12893818.

[entrez-6] "Entrez Gene: E2F7 E2F transcription factor 7".

[7] Di Stefano, L., Jensen, M. R., Helin, K. E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes. EMBO J. 22: 6289-6298, 2003. PubMed: 14633988

[8] Bruin, A., Maiti, B., Jakoi, L., Timmers, C., Buerki, R., Leone, G. Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation. J. Biol. Chem. 278: 42041-42049, 2003. PubMed: 12893818

[UniProt-9] "UniProt, Q96AV8". Pristupljeno 7. 8. 2021.

[10] Li, J., Ran, C., Li, E., Gordon, F., Comstock, G., Siddiqui, H., Cleghorn, W., Chen, H.-Z., Kornacker, K., Liu, C.-G., Pandit, S. K., Khanizadeh, M., Weinstein, M., Leone, G., de Bruin, A. Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Dev. Cell 14: 62-75, 2008. PubMed: 18194653

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