組蛋白密碼

組蛋白密碼（Histone code）是一個描述真核生物藉修飾包裹DNA的組蛋白（主要是其N端尾）以調控基因表現的理論，和DNA甲基化共同組成表觀遺傳密碼（英语：epigenetic code）^[2] 。組蛋白上的修飾包括乙醯化、甲基化、磷酸化、泛素化、二磷酸腺苷核糖基化、GlcNAc糖基化（英语：GlcNAc）^[3]、瓜氨酸化、脯胺酸異構化（英语：Proline isomerization in epigenetics）^[4]與SUMO修飾（英语：SUMO protein）等^[5]，這些修飾的組合可影響染色體結構以及與其他蛋白的結合力，提升或降低基因的轉錄。人類細胞中組蛋白修飾的種類複雜，其中某幾種修飾可能傾向出現在同一個組蛋白上^[6]。近年由於質譜法技術的發展而有更多修飾種類與位點被發現^[7]，也有許多研究探討加上或移除組蛋白修飾的多種酵素，以及可辨認這些修飾而與之結合的其他蛋白^[8]。

種類

組蛋白修飾對基因轉錄的影響
修飾種類	組蛋白位點
修飾種類	H3K4	H3K9	H3K14	H3K27	H3K79	H3K36	H4K20	H2BK5	H2BK20
單甲基化	促進^[9]	促進^[10]		促進^[10]	促進^[10]^[11]		促進^[10]	促進^[10]
雙甲基化		抑制^[12]		抑制^[12]	促進^[11]
三甲基化	促進^[13]	抑制^[10]		抑制^[10]	促進^[11] 抑制^[10]	促進		抑制^[12]
乙醯化	促進^[14]	促進^[13]	促進^[13]	促進^[15]					促進

參考文獻

^ Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology.. Nat Med. 2011, 17 (3): 330–9. PMID 21386836. doi:10.1038/nm.2305.
^ Jenuwein T, Allis C. Translating the histone code. Science. 2001, 293 (5532): 1074–80. PMID 11498575. doi:10.1126/science.1063127.
^ K, Sakabe; Z, Wang; Gw, Hart. Beta-N-acetylglucosamine (O-GlcNAc) Is Part of the Histone Code. Proceedings of the National Academy of Sciences of the United States of America. 2010-11-16, 107 (46): 19915–20. Bibcode:2010PNAS..10719915S. PMC 2993388 . PMID 21045127. doi:10.1073/pnas.1009023107.
^ Nelson CJ, Santos-Rosa H, Kouzarides T. Proline isomerization of histone H3 regulates lysine methylation and gene expression. Cell. September 2006, 126 (5): 905–16. PMID 16959570. doi:10.1016/j.cell.2006.07.026.
^ Nathan D, Ingvarsdottir K, Sterner DE, et al. Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev. April 2006, 20 (8): 966–76. PMC 1472304 . PMID 16598039. doi:10.1101/gad.1404206.
^ Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, et al. Combinatorial patterns of histone acetylations and methylations in the human genome.. Nat Genet. 2008, 40 (7): 897–903. PMC 2769248 . PMID 18552846. doi:10.1038/ng.154.
^ Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.. Cell. 2011, 146 (6): 1016–28. PMC 3176443 . PMID 21925322. doi:10.1016/j.cell.2011.08.008.
^ Wang M, Mok MW, Harper H, Lee WH, Min J, Knapp S, Oppermann U, Marsden B, Schapira M. Structural Genomics of Histone Tail Recognition. Bioinformatics. 24 Aug 2010, 26 (20): 2629–2630. PMC 2951094 . PMID 20739309. doi:10.1093/bioinformatics/btq491.
^ Benevolenskaya EV. Histone H3K4 demethylases are essential in development and differentiation. Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. August 2007, 85 (4): 435–43. PMID 17713579. doi:10.1139/o07-057.
^ ^10.0 ^10.1 ^10.2 ^10.3 ^10.4 ^10.5 ^10.6 ^10.7 Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. May 2007, 129 (4): 823–37. PMID 17512414. doi:10.1016/j.cell.2007.05.009.
^ ^11.0 ^11.1 ^11.2 Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, et al. DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Molecular and Cellular Biology. April 2008, 28 (8): 2825–39. PMC 2293113 . PMID 18285465. doi:10.1128/MCB.02076-07.
^ ^12.0 ^12.1 ^12.2 Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ. Determination of enriched histone modifications in non-genic portions of the human genome. BMC Genomics. March 2009, 10: 143. PMC 2667539 . PMID 19335899. doi:10.1186/1471-2164-10-143.
^ ^13.0 ^13.1 ^13.2 Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, et al. The landscape of histone modifications across 1% of the human genome in five human cell lines. Genome Research. June 2007, 17 (6): 691–707. PMC 1891331 . PMID 17567990. doi:10.1101/gr.5704207.
^ Guillemette B, Drogaris P, Lin HH, Armstrong H, Hiragami-Hamada K, Imhof A, et al. H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation. PLoS Genetics. March 2011, 7 (3): e1001354. PMC 3069113 . PMID 21483810. doi:10.1371/journal.pgen.1001354.
^ Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proceedings of the National Academy of Sciences of the United States of America. December 2010, 107 (50): 21931–6. PMC 3003124 . PMID 21106759. doi:10.1073/pnas.1016071107.

[pmid21386836-1] Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology.. Nat Med. 2011, 17 (3): 330–9. PMID 21386836. doi:10.1038/nm.2305.

[Jenuwein-2] Jenuwein T, Allis C. Translating the histone code. Science. 2001, 293 (5532): 1074–80. PMID 11498575. doi:10.1126/science.1063127.

[3] K, Sakabe; Z, Wang; Gw, Hart. Beta-N-acetylglucosamine (O-GlcNAc) Is Part of the Histone Code. Proceedings of the National Academy of Sciences of the United States of America. 2010-11-16, 107 (46): 19915–20. Bibcode:2010PNAS..10719915S. PMC 2993388 . PMID 21045127. doi:10.1073/pnas.1009023107.

[4] Nelson CJ, Santos-Rosa H, Kouzarides T. Proline isomerization of histone H3 regulates lysine methylation and gene expression. Cell. September 2006, 126 (5): 905–16. PMID 16959570. doi:10.1016/j.cell.2006.07.026.

[5] Nathan D, Ingvarsdottir K, Sterner DE, et al. Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev. April 2006, 20 (8): 966–76. PMC 1472304 . PMID 16598039. doi:10.1101/gad.1404206.

[pmid18552846-6] Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, et al. Combinatorial patterns of histone acetylations and methylations in the human genome.. Nat Genet. 2008, 40 (7): 897–903. PMC 2769248 . PMID 18552846. doi:10.1038/ng.154.

[pmid21925322-7] Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.. Cell. 2011, 146 (6): 1016–28. PMC 3176443 . PMID 21925322. doi:10.1016/j.cell.2011.08.008.

[Wang-8] Wang M, Mok MW, Harper H, Lee WH, Min J, Knapp S, Oppermann U, Marsden B, Schapira M. Structural Genomics of Histone Tail Recognition. Bioinformatics. 24 Aug 2010, 26 (20): 2629–2630. PMC 2951094 . PMID 20739309. doi:10.1093/bioinformatics/btq491.

[Benevolenskaya_2007-9] Benevolenskaya EV. Histone H3K4 demethylases are essential in development and differentiation. Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. August 2007, 85 (4): 435–43. PMID 17713579. doi:10.1139/o07-057.

[Barski_2007-10] 10.0 ^10.1 ^10.2 ^10.3 ^10.4 ^10.5 ^10.6 ^10.7 Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. May 2007, 129 (4): 823–37. PMID 17512414. doi:10.1016/j.cell.2007.05.009.

[Steger_2008-11] 11.0 ^11.1 ^11.2 Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, et al. DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Molecular and Cellular Biology. April 2008, 28 (8): 2825–39. PMC 2293113 . PMID 18285465. doi:10.1128/MCB.02076-07.

[Rosenfeld_2009-12] 12.0 ^12.1 ^12.2 Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ. Determination of enriched histone modifications in non-genic portions of the human genome. BMC Genomics. March 2009, 10: 143. PMC 2667539 . PMID 19335899. doi:10.1186/1471-2164-10-143.

[Koch_2007-13] 13.0 ^13.1 ^13.2 Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, et al. The landscape of histone modifications across 1% of the human genome in five human cell lines. Genome Research. June 2007, 17 (6): 691–707. PMC 1891331 . PMID 17567990. doi:10.1101/gr.5704207.

[Guillemette_2011-14] Guillemette B, Drogaris P, Lin HH, Armstrong H, Hiragami-Hamada K, Imhof A, et al. H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation. PLoS Genetics. March 2011, 7 (3): e1001354. PMC 3069113 . PMID 21483810. doi:10.1371/journal.pgen.1001354.

[Creyghton_2010-15] Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proceedings of the National Academy of Sciences of the United States of America. December 2010, 107 (50): 21931–6. PMC 3003124 . PMID 21106759. doi:10.1073/pnas.1016071107.

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組蛋白密碼

種類

參考文獻

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