Brpf1
Peregrin, znan i kao bromodomen i protein 1 sa PHD-prstom i jest protein koji je kod ljudi kodiran genom BRPF1 sa hromosoma 3,pozicija p26-p25. Peregrin je multivalentni hromatinski regulator koji prepoznaje različite epigenetičke oznake i aktivira tri histon-transferaze (Moz, Morf i Hbo1). BRPF1 sadrži dva PHD-prsta, jedan bromodomen i jedan hhromo/Tudor-vezani Pro-Trp-Trp-Pro (PWWP) domen.
Funkcija[uredi | uredi izvor]
Razvoj embriona[uredi | uredi izvor]
Brpf1 gen je veoma konzerviran i ima ključnu ulogu u različitim razvojnim procesima.[2][3][4] Zebricin BRPF1, koji je koordiniran svojim posebnim skupom PWWP domena, posreduje acetilaciju histona, zavisnu od "Moz" i održava ekspresiju Hox gena tokom razvoja kičmenjaka, stoga određuje odgovarajući ždrijelni segmentni identiteti.[6] Nadalje, Brpf1 može imati značajnu ulogu ne samo u održavanju prednje-zadnje ose kraniofacijalnog, već i dorzalno-ventralne ose kaudalnog skeleta.[7] Nedavne studije su pokazale da ablacija "Brpf1" gena miša uzrokuje smrtnost embriona na dan embriona 9,5.[3][4] Konkretno, "Brpf1" regulira placentna vaskularna formacija, zatvaranje nervne cijevi, primitivna hematopoeza i proliferacija embriondkih fibroblasta.[3][4] Za centralni nervni sistem, Brpf1 ima visoku ekspresiju i neophodan je za razvoj nekoliko važnih struktura, uključujući neokorteks i dentatni girus u hipokampusu.[3] Brpf1 je dinamički izražen tokom razvoja prednjeg mozga, posebno hipokampusne neurogeneze.[5] Brpf1 dijeli fenotip sa transkripcijskim faktorimasSox2, Tlx i Tbr2 u razvoju dentatnom girusu i ima potencijalnu vezu sa nervnim matičnim i progenitorskim ćelijama.[5] Osim prednjeg mozga, Brpf1 je također potreban za pravilno oblikovanje kraniofacijske hrskavice, koja je izvedena iz ćelija nervnog grebena koje migriraju iz zadnjeg mozga.[8]
Razvoj kancera[uredi | uredi izvor]
Nedavno je objavljeno da Brpf1 ima ulogu tumorskog supresora ili onkogenu ulogu u nekoliko malignih tumora, uključujući leukemiju, meduloblastom i endometrijski stromni sarkom.[2][9][10][11] Brpf1 se smatrao genom supresorom tumora jer se čini da mutacije u ćelijama raka smanjuju funkciju Brpf1[9][10] Međutim, onkogena uloga Brpf1 je moguća i kod raka. Naprimjer, Brpf1 može formirati stabilan kompleks sa Moz-Tif2, što bi moglo dovesti do razvoja ljudske akutne mijeloidne leukemije (AML).[11] Postoji još jedan srodni kompleks Brpf1 Brpf1–Ing5–Eaf6, koji također ima direktnu ulogu u nastanku raka.[2]
Također poglegajte[uredi | uredi izvor]
Reference[uredi | uredi izvor]
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d Yang XJ (2015). "MOZ and MORF acetyltransferases: Molecular interaction, animal development and human disease". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1853 (8): 1818–26. doi:10.1016/j.bbamcr.2015.04.014. PMID 25920810.
- ^ a b c d e You L, Chen L, Penney J, Miao D, Yang XJ (2014). "Expression atlas of the multivalent epigenetic regulator Brpf1 and its requirement for survival of mouse embryos". Epigenetics. 9 (6): 860–72. doi:10.4161/epi.28530. PMC 4065184. PMID 24646517.
- ^ a b c d You L, Yan K, Zou J, Zhao H, Bertos NR, Park M, Wang E, Yang XJ (2015). "The chromatin regulator Brpf1 regulates embryo development and cell proliferation". The Journal of Biological Chemistry. 290 (18): 11349–64. doi:10.1074/jbc.M115.643189. PMC 4416840. PMID 25773539.
- ^ a b c You L, Yan K, Zou J, Zhou J, Zhao H, Bertos NR, Park M, Wang E, Yang XJ (2015). "The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors". PLOS Genetics. 11 (3): e1005034. doi:10.1371/journal.pgen.1005034. PMC 4355587. PMID 25757017.
- ^ Laue K, Daujat S, Crump JG, Plaster N, Roehl HH, Kimmel CB, Schneider R, Hammerschmidt M (2008). "The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity". Development. 135 (11): 1935–46. doi:10.1242/dev.017160. PMC 2919486. PMID 18469222.
- ^ Hibiya K, Katsumoto T, Kondo T, Kitabayashi I, Kudo A (2009). "Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons". Developmental Biology. 329 (2): 176–90. doi:10.1016/j.ydbio.2009.02.021. PMID 19254709.
- ^ Yan K, You L, Degerny C, Ghorbani M, Liu X, Chen L, Li L, Miao D, Yang XJ (2016). "The Chromatin Regulator BRPF3 Preferentially Activates the HBO1 Acetyltransferase but Is Dispensable for Mouse Development and Survival". The Journal of Biological Chemistry. 291 (6): 2647–63. doi:10.1074/jbc.M115.703041. PMC 4742735. PMID 26677226.
- ^ a b Kool M, Jones DT, Jäger N, Northcott PA, Pugh TJ, Hovestadt V, et al. (2014). "Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition". Cancer Cell. 25 (3): 393–405. doi:10.1016/j.ccr.2014.02.004. PMC 4493053. PMID 24651015.
- ^ a b Huether R, Dong L, Chen X, Wu G, Parker M, Wei L, et al. (2014). "The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes". Nature Communications. 5: 3630. doi:10.1038/ncomms4630. PMC 4119022. PMID 24710217.
- ^ a b Shima H, Yamagata K, Aikawa Y, Shino M, Koseki H, Shimada H, Kitabayashi I (2014). "Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion". International Journal of Hematology. 99 (1): 21–31. doi:10.1007/s12185-013-1466-x. PMID 24258712. S2CID 207400403.
Dopunska literatura[uredi | uredi izvor]
- Klein BJ, Muthurajan UM, Lalonde ME, Gibson MD, Andrews FH, Hepler M, Machida S, Yan K, Kurumizaka H, Poirier MG, Côté J, Luger K, Kutateladze TG (Jan 2016). "Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation". Nucleic Acids Research. 44 (1): 472–84. doi:10.1093/nar/gkv1321. PMC 4705663. PMID 26626149.
- You L, Zou J, Zhao H, Bertos NR, Park M, Wang E, Yang XJ (Mar 2015). "Deficiency of the chromatin regulator BRPF1 causes abnormal brain development". The Journal of Biological Chemistry. 290 (11): 7114–29. doi:10.1074/jbc.M114.635250. PMC 4358132. PMID 25568313.
- Lubula MY, Eckenroth BE, Carlson S, Poplawski A, Chruszcz M, Glass KC (Nov 2014). "Structural insights into recognition of acetylated histone ligands by the BRPF1 bromodomain". FEBS Letters. 588 (21): 3844–54. doi:10.1016/j.febslet.2014.09.028. PMC 4252766. PMID 25281266.
- Carlson S, Glass KC (Nov 2014). "The MOZ histone acetyltransferase in epigenetic signaling and disease". Journal of Cellular Physiology. 229 (11): 1571–4. doi:10.1002/jcp.24617. PMC 4750494. PMID 24633655.
- Poplawski A, Hu K, Lee W, Natesan S, Peng D, Carlson S, Shi X, Balaz S, Markley JL, Glass KC (Apr 2014). "Molecular insights into the recognition of N-terminal histone modifications by the BRPF1 bromodomain". Journal of Molecular Biology. 426 (8): 1661–76. doi:10.1016/j.jmb.2013.12.007. PMC 3969779. PMID 24333487.
- Qin S, Jin L, Zhang J, Liu L, Ji P, Wu M, Wu J, Shi Y (Oct 2011). "Recognition of unmodified histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein (MOZ) and MOZ-related factor (MORF)". The Journal of Biological Chemistry. 286 (42): 36944–55. doi:10.1074/jbc.M111.244400. PMC 3196140. PMID 21880731.
- Mishima Y, Miyagi S, Saraya A, Negishi M, Endoh M, Endo TA, Toyoda T, Shinga J, Katsumoto T, Chiba T, Yamaguchi N, Kitabayashi I, Koseki H, Iwama A (Sep 2011). "The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis". Blood. 118 (9): 2443–53. doi:10.1182/blood-2011-01-331892. PMID 21753189.
- Vezzoli A, Bonadies N, Allen MD, Freund SM, Santiveri CM, Kvinlaug BT, Huntly BJ, Göttgens B, Bycroft M (maj 2010). "Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1". Nature Structural & Molecular Biology. 17 (5): 617–9. doi:10.1038/nsmb.1797. PMID 20400950. S2CID 38082800.
- Hibiya K, Katsumoto T, Kondo T, Kitabayashi I, Kudo A (maj 2009). "Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons". Developmental Biology. 329 (2): 176–90. doi:10.1016/j.ydbio.2009.02.021. PMID 19254709.
- Ullah M, Pelletier N, Xiao L, Zhao SP, Wang K, Degerny C, Tahmasebi S, Cayrou C, Doyon Y, Goh SL, Champagne N, Côté J, Yang XJ (Nov 2008). "Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexes". Molecular and Cellular Biology. 28 (22): 6828–43. doi:10.1128/MCB.01297-08. PMC 2573306. PMID 18794358.
- Poplawski A, Hu K, Lee W, Natesan S, Peng D, Carlson S, Shi X, Balaz S, Markley JL, Glass KC (Apr 2014). "Molecular insights into the recognition of N-terminal histone modifications by the BRPF1 bromodomain". Journal of Molecular Biology. 426 (8): 1661–76. doi:10.1016/j.jmb.2013.12.007. PMC 3969779. PMID 24333487.
Vanjski linkovi[uredi | uredi izvor]
- Lokacija ljudskog genoma BRPF1 i stranica sa detaljima o genu BRPF1 u UCSC Genome Browseru.