Biology:EP300
From HandWiki
Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene.[1] It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.
The EP300 gene is located on the long (q) arm of the human chromosome 22 at position 13.2. This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein.
EP300 is closely related to another gene, CREB binding protein, which is found on human chromosome 16.
Function
p300 HAT functions as histone acetyltransferase[2] that regulates transcription via chromatin remodeling, and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein.
p300 HAT contains a bromodomain which is involved in IL6 signaling.[3]: 3.1
This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and, thus, plays a role in the stimulation of hypoxia-induced genes such as VEGF.[4]
Mechanism
The p300 protein carries out its function of activating transcription by binding to transcription factors, and the transcription machinery. On the basis of this function, p300 is called a transcriptional coactivator. The p300 interaction with transcription factors is managed by one or more of p300 domains: the nuclear receptor interaction domain (RID), the KIX domain (CREB and MYB interaction domain), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). The last four domains, KIX, TAZ1, TAZ2 and IBiD of p300, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53.[5]
Clinical significance
Mutations in the EP300 gene are responsible for a small percentage of cases of Rubinstein-Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein-Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.[6][7]
Interactions
EP300 has been shown to interact with:
- BCL3,[8]
- BRCA1,[9][10]
- CDX2,[11]
- CEBPB,[12]
- CITED1,[13]
- CITED2,[14][15][16][17]
- DDX5,[18]
- DTX1,[19]
- EID1,[20][21]
- ELK1,[22]
- ESR1,[9][23][24]
- FEN1,[25]
- GPS2,[26]
- HIF1A,[27][28]
- HNF1A,[29]
- HNRPU,[30]
- ING4,[31]
- ING5,[31]
- IRF2,[32]
- LEF1,[33]
- MAF,[34]
- MAML1,[35][36]
- MEF2C,[37]
- MEF2D,[38][39]
- MYBL2,[40]
- Mdm2,[41]
- MyoD,[37][42]
- MEF2A,[43]
- NCOA6,[44]
- NFATC2,[45]
- NPAS2,[46]
- P53,[41][47][48][49][50]
- PAX6,[11]
- PCNA,[51]
- POLI, [52]
- PROX1,[34]
- PTMA,[53]
- PPARA,[54][55]
- PPARG,[23]
- RORA,[42]
- RELA,[56][57]
- SMAD1,[58][59]
- SMAD2,[60][61]
- SMAD7,[62]
- SNIP1,[63]
- SS18,[64]
- STAT3,[59]
- STAT6,[65]
- TAL1,[66]
- TCF3,[67]
- TFAP2A,[15]
- TGS1,[68]
- TRERF1,[69]
- TSG101,[70]
- THRA,[43]
- TWIST1,[71]
- YY1,[72][73] and
- Zif268.[74]
References
- ↑ "Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor". Genes & Development 8 (8): 869–884. April 1994. doi:10.1101/gad.8.8.869. PMID 7523245.
- ↑ "The transcriptional coactivators p300 and CBP are histone acetyltransferases". Cell 87 (5): 953–959. November 1996. doi:10.1016/S0092-8674(00)82001-2. PMID 8945521.
- ↑ "Bromodomains: Translating the words of lysine acetylation into myelin injury and repair". Neuroscience Letters 625: 4–10. June 2016. doi:10.1016/j.neulet.2015.10.015. PMID 26472704.
- ↑ "Entrez Gene: EP300". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2033.
- ↑ "Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53". Proceedings of the National Academy of Sciences of the United States of America 104 (17): 7009–7014. April 2007. doi:10.1073/pnas.0702010104. PMID 17438265. Bibcode: 2007PNAS..104.7009T.; "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics 89 (6): 756–768. June 2007. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953.
- ↑ "Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease". American Journal of Human Genetics 76 (4): 572–580. April 2005. doi:10.1086/429130. PMID 15706485.
- ↑ "Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300". Journal of Medical Genetics 44 (5): 327–333. May 2007. doi:10.1136/jmg.2006.046698. PMID 17220215.
- ↑ "Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation". The Journal of Biological Chemistry 274 (40): 28491–28496. October 1999. doi:10.1074/jbc.274.40.28491. PMID 10497212.
- ↑ 9.0 9.1 "p300 Modulates the BRCA1 inhibition of estrogen receptor activity". Cancer Research 62 (1): 141–151. January 2002. PMID 11782371.
- ↑ "CBP/p300 interact with and function as transcriptional coactivators of BRCA1". Proceedings of the National Academy of Sciences of the United States of America 97 (3): 1020–1025. February 2000. doi:10.1073/pnas.97.3.1020. PMID 10655477. Bibcode: 2000PNAS...97.1020P.
- ↑ 11.0 11.1 "Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator". The Journal of Biological Chemistry 274 (41): 28950–28957. October 1999. doi:10.1074/jbc.274.41.28950. PMID 10506141.
- ↑ "Interaction and functional collaboration of p300 and C/EBPbeta". Molecular and Cellular Biology 17 (11): 6609–6617. November 1997. doi:10.1128/mcb.17.11.6609. PMID 9343424.
- ↑ "The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors". The Journal of Biological Chemistry 275 (12): 8825–8834. March 2000. doi:10.1074/jbc.275.12.8825. PMID 10722728.
- ↑ "Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1". Genes & Development 13 (1): 64–75. January 1999. doi:10.1101/gad.13.1.64. PMID 9887100.
- ↑ 15.0 15.1 "Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2". The Journal of Biological Chemistry 278 (18): 16021–16029. May 2003. doi:10.1074/jbc.M208144200. PMID 12586840.
- ↑ "Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2". The Journal of Biological Chemistry 277 (10): 8559–8565. March 2002. doi:10.1074/jbc.M110850200. PMID 11744733.
- ↑ "MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression". The Journal of Biological Chemistry 274 (51): 36159–36167. December 1999. doi:10.1074/jbc.274.51.36159. PMID 10593900.
- ↑ "Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300". Oncogene 22 (1): 151–156. January 2003. doi:10.1038/sj.onc.1206067. PMID 12527917.
- ↑ "Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor". The Journal of Biological Chemistry 276 (48): 45031–45040. November 2001. doi:10.1074/jbc.M105245200. PMID 11564735.
- ↑ "Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle". Molecular and Cellular Biology 20 (23): 8889–8902. December 2000. doi:10.1128/mcb.20.23.8889-8902.2000. PMID 11073989.
- ↑ "A novel Rb- and p300-binding protein inhibits transactivation by MyoD". Molecular and Cellular Biology 20 (23): 8903–8915. December 2000. doi:10.1128/mcb.20.23.8903-8915.2000. PMID 11073990.
- ↑ "MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300". The EMBO Journal 22 (2): 281–291. January 2003. doi:10.1093/emboj/cdg028. PMID 12514134.
- ↑ 23.0 23.1 "The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation". Developmental Cell 3 (6): 903–910. December 2002. doi:10.1016/s1534-5807(02)00360-x. PMID 12479814.
- ↑ "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proceedings of the National Academy of Sciences of the United States of America 99 (5): 2642–2647. March 2002. doi:10.1073/pnas.261715899. PMID 11867769. Bibcode: 2002PNAS...99.2642K.
- ↑ "Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300". Molecular Cell 7 (6): 1221–1231. June 2001. doi:10.1016/s1097-2765(01)00272-6. PMID 11430825.
- ↑ "AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins". Journal of Virology 74 (13): 5872–5879. July 2000. doi:10.1128/jvi.74.13.5872-5879.2000. PMID 10846067.
- ↑ "Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch". Science 295 (5556): 858–861. February 2002. doi:10.1126/science.1068592. PMID 11823643. Bibcode: 2002Sci...295..858L.
- ↑ "Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha". Proceedings of the National Academy of Sciences of the United States of America 99 (8): 5367–5372. April 2002. doi:10.1073/pnas.082117899. PMID 11959990. Bibcode: 2002PNAS...99.5367F.
- ↑ "Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter". Diabetes 51 (5): 1409–1418. May 2002. doi:10.2337/diabetes.51.5.1409. PMID 11978637.
- ↑ "Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes". Molecular and Cellular Biology 22 (8): 2598–2606. April 2002. doi:10.1128/mcb.22.8.2598-2606.2002. PMID 11909954.
- ↑ 31.0 31.1 "p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity". Cancer Research 63 (10): 2373–2378. May 2003. PMID 12750254.
- ↑ "Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells following phorbol ester treatment". The Journal of Biological Chemistry 276 (24): 20973–20980. June 2001. doi:10.1074/jbc.M101707200. PMID 11304541.
- ↑ "Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4". The Journal of Biological Chemistry 278 (6): 3776–3785. February 2003. doi:10.1074/jbc.M210081200. PMID 12446687.
- ↑ 34.0 34.1 "CREB-binding protein/p300 co-activation of crystallin gene expression". The Journal of Biological Chemistry 277 (27): 24081–24089. July 2002. doi:10.1074/jbc.M201821200. PMID 11943779.
- ↑ "p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro". Molecular and Cellular Biology 22 (22): 7812–7819. November 2002. doi:10.1128/mcb.22.22.7812-7819.2002. PMID 12391150.
- ↑ "Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex". Genes & Development 16 (11): 1397–1411. June 2002. doi:10.1101/gad.991602. PMID 12050117.
- ↑ 37.0 37.1 "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C". Molecular and Cellular Biology 17 (2): 1010–1026. February 1997. doi:10.1128/mcb.17.2.1010. PMID 9001254.
- ↑ "Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4". The Journal of Biological Chemistry 275 (29): 22563–22567. July 2000. doi:10.1074/jbc.C000304200. PMID 10825153.
- ↑ "Cabin1 represses MEF2-dependent Nur77 expression and T cell apoptosis by controlling association of histone deacetylases and acetylases with MEF2". Immunity 13 (1): 85–94. July 2000. doi:10.1016/s1074-7613(00)00010-8. PMID 10933397.
- ↑ "Effects of B-Myb on gene transcription: phosphorylation-dependent activity ans acetylation by p300". The Journal of Biological Chemistry 277 (6): 4088–4097. February 2002. doi:10.1074/jbc.M105112200. PMID 11733503.
- ↑ 41.0 41.1 "p300/MDM2 complexes participate in MDM2-mediated p53 degradation". Molecular Cell 2 (4): 405–415. October 1998. doi:10.1016/s1097-2765(00)80140-9. PMID 9809062.
- ↑ 42.0 42.1 "Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD". Nucleic Acids Research 27 (2): 411–420. January 1999. doi:10.1093/nar/27.2.411. PMID 9862959.
- ↑ 43.0 43.1 "p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor". The Biochemical Journal 369 (Pt 3): 477–484. February 2003. doi:10.1042/BJ20020057. PMID 12371907.
- ↑ "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proceedings of the National Academy of Sciences of the United States of America 97 (11): 6212–6217. May 2000. doi:10.1073/pnas.97.11.6212. PMID 10823961. Bibcode: 2000PNAS...97.6212K.
- ↑ "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". The Journal of Experimental Medicine 187 (12): 2031–2036. June 1998. doi:10.1084/jem.187.12.2031. PMID 9625762.
- ↑ "Histone acetyltransferase-dependent chromatin remodeling and the vascular clock". The Journal of Biological Chemistry 279 (8): 7091–7097. February 2004. doi:10.1074/jbc.M311973200. PMID 14645221.
- ↑ "Recruitment of p300/CBP in p53-dependent signal pathways". Cell 89 (7): 1175–1184. June 1997. doi:10.1016/s0092-8674(00)80304-9. PMID 9215639.
- ↑ "Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53". Cell 117 (6): 735–748. June 2004. doi:10.1016/j.cell.2004.05.009. PMID 15186775.
- ↑ "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene". The Journal of Biological Chemistry 275 (45): 34938–34945. November 2000. doi:10.1074/jbc.M005411200. PMID 10942770.
- ↑ "p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300". The Journal of Biological Chemistry 277 (11): 9054–9061. March 2002. doi:10.1074/jbc.M108870200. PMID 11782467.
- ↑ "Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis". Nature 410 (6826): 387–391. March 2001. doi:10.1038/35066610. PMID 11268218. Bibcode: 2001Natur.410..387H.
- ↑ "DNA polymerase ι is acetylated in response to sN2 alkylating agents". Scientific Reports 9 (1): 4789. March 2019. doi:10.1038/s41598-019-41249-3. PMID 30886224.
- ↑ "Epstein-Barr virus nuclear antigen 3C and prothymosin alpha interact with the p300 transcriptional coactivator at the CH1 and CH3/HAT domains and cooperate in regulation of transcription and histone acetylation". Journal of Virology 76 (10): 4699–4708. May 2002. doi:10.1128/jvi.76.10.4699-4708.2002. PMID 11967287.
- ↑ "p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha". The Journal of Biological Chemistry 272 (52): 33435–33443. December 1997. doi:10.1074/jbc.272.52.33435. PMID 9407140.
- ↑ "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". The Journal of Biological Chemistry 274 (22): 15901–15907. May 1999. doi:10.1074/jbc.274.22.15901. PMID 10336495.
- ↑ "Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65". The Journal of Biological Chemistry 278 (4): 2758–2766. January 2003. doi:10.1074/jbc.M209572200. PMID 12419806.
- ↑ "CREB-binding protein/p300 are transcriptional coactivators of p65". Proceedings of the National Academy of Sciences of the United States of America 94 (7): 2927–2932. April 1997. doi:10.1073/pnas.94.7.2927. PMID 9096323. Bibcode: 1997PNAS...94.2927G.
- ↑ "Activation of Smad1-mediated transcription by p300/CBP". Biochimica et Biophysica Acta 1489 (2–3): 354–364. December 1999. doi:10.1016/S0167-4781(99)00166-9. PMID 10673036.
- ↑ 59.0 59.1 "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300". Science 284 (5413): 479–482. April 1999. doi:10.1126/science.284.5413.479. PMID 10205054. Bibcode: 1999Sci...284..479N.
- ↑ "A Smad transcriptional corepressor". Cell 97 (1): 29–39. April 1999. doi:10.1016/S0092-8674(00)80712-6. PMID 10199400.
- ↑ "c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity". Proceedings of the National Academy of Sciences of the United States of America 98 (11): 6198–6203. May 2001. doi:10.1073/pnas.101579798. PMID 11371641. Bibcode: 2001PNAS...98.6198P.
- ↑ "Control of Smad7 stability by competition between acetylation and ubiquitination". Molecular Cell 10 (3): 483–493. September 2002. doi:10.1016/s1097-2765(02)00639-1. PMID 12408818.
- ↑ "A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction". Genes & Development 14 (13): 1605–1616. July 2000. doi:10.1101/gad.14.13.1605. PMID 10887155.
- ↑ "p300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion". Cell 102 (6): 839–848. September 2000. doi:10.1016/s0092-8674(00)00072-6. PMID 11030627.
- ↑ "Cooperation of the transcriptional coactivators CBP and p300 with Stat6". Journal of Interferon & Cytokine Research 19 (7): 711–722. July 1999. doi:10.1089/107999099313550. PMID 10454341.
- ↑ "p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein". Oncogene 18 (35): 4958–4967. September 1999. doi:10.1038/sj.onc.1202889. PMID 10490830.
- ↑ "Regulation of E2A activities by histone acetyltransferases in B lymphocyte development". The Journal of Biological Chemistry 278 (4): 2370–2376. January 2003. doi:10.1074/jbc.M211464200. PMID 12435739.
- ↑ "Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation". The Journal of Biological Chemistry 277 (22): 20011–20019. May 2002. doi:10.1074/jbc.M201739200. PMID 11912212.
- ↑ "A novel zinc finger protein TReP-132 interacts with CBP/p300 to regulate human CYP11A1 gene expression". The Journal of Biological Chemistry 276 (36): 33881–33892. September 2001. doi:10.1074/jbc.M100113200. PMID 11349124.
- ↑ "Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300". Cancer 86 (4): 689–696. August 1999. doi:10.1002/(sici)1097-0142(19990815)86:4<689::aid-cncr19>3.0.co;2-p. PMID 10440698.
- ↑ "Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A". Cell 96 (3): 405–413. February 1999. doi:10.1016/S0092-8674(00)80553-X. PMID 10025406.
- ↑ "Regulation of transcription factor YY1 by acetylation and deacetylation". Molecular and Cellular Biology 21 (17): 5979–5991. September 2001. doi:10.1128/mcb.21.17.5979-5991.2001. PMID 11486036.
- ↑ "Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300". Genes & Development 9 (10): 1188–1198. May 1995. doi:10.1101/gad.9.10.1188. PMID 7758944.
- ↑ "cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)". The Biochemical Journal 336 ( Pt 1) (Pt 1): 183–189. November 1998. doi:10.1042/bj3360183. PMID 9806899.
Further reading
- "Synergistic role of E1A-binding proteins and tissue-specific transcription factors in differentiation". Journal of Cellular Biochemistry 67 (4): 423–431. December 1997. doi:10.1002/(SICI)1097-4644(19971215)67:4<423::AID-JCB1>3.0.CO;2-U. PMID 9383702.
- "Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator". IUBMB Life 51 (3): 175–181. March 2001. doi:10.1080/152165401753544241. PMID 11547919.
- "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA and Cell Biology 23 (4): 193–205. April 2004. doi:10.1089/104454904773819789. PMID 15142377.
- "Tat acetylation: a regulatory switch between early and late phases in HIV transcription elongation". Reversible Protein Acetylation. Novartis Foundation Symposia. 259. 2004. pp. 182–93; discussion 193–6, 223–5. doi:10.1002/0470862637.ch13. ISBN 978-0-470-86263-6.
- "The Vpr protein from HIV-1: distinct roles along the viral life cycle". Retrovirology 2. February 2005. doi:10.1186/1742-4690-2-11. PMID 15725353.
External links
- GeneReviews/NCBI/NIH/UW entry on Rubinstein-Taybi Syndrome
- GeneCard
- EP300+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- NURSA C54
- FactorBook P300
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
PDB gallery | |
|---|---|
|
 |  |
