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研究生:劉又瑜
研究生(外文):You-Yu Liu
論文名稱:SUV39H1 和 G9a 參與 M33 誘導異染色質形成之探討
論文名稱(外文):The study of M33-induced heterochromatin formation through SUV39H1 and G9a
指導教授:楊文明 博士
口試委員:姚雅莉 博士廖泓鈞 博士
口試日期:2016-07-26
學位類別:碩士
校院名稱:國立中興大學
系所名稱:分子生物學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:62
中文關鍵詞:M33SUV39H1G9a異染色質形成
外文關鍵詞:M33SUV39H1G9aheterochromatin formation
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異染色質結構對維持基因體穩定性扮演重要角色,研究發現早老症 (progeria) 病患細胞中染色質結構變鬆散,使細胞走向老化,顯示異染色質形成對於維持細胞 正常運作很重要。目前已知兩種異染色質形成機制,其一是由 histone methyltransferase (HMT) SUV39H1 及 G9a 甲基化 histone H3 lysine 9 (H3K9),使 HP1結合H3K9me3,進而形成異染色質;另一是由 polycombgroup(PcG) 調控, PcG 主要分為 polycomb repressive complex 1 (PRC1) 及 PRC2,PRC2 中的 HMT 甲 基化 H3K27,接著 PRC1 中 chromobox (CBX) 結合 H3K27me3,使異染色質形成。 M33 是 CBX2 的同源蛋白,本實驗室發現 M33 能夠誘導 DAPI dots 形成,又 M33 誘導的 DAPI dots 與異染色質標記 H3K9me3 及 H3K27me2 重疊,且 M33 具有轉 錄抑制活性,顯示 M33 具有誘導異染色質形成的能力,然而,此現象未見於其他 CBX 蛋白,暗示 M33 可能除一般 CBX 參與 PcG-mediated 的機制,還具有其他方 式使異染色質形成。研究已知 M33 除結合 H3K27me3 外,其 chromodomain 亦能 夠結合 H3K9me3 ,我們推測 M33 可能透過 PcG-mediated 的方式或是 SUV39H1 和 G9a 的參與,使異染色質形成,但是此方面的研究仍不清楚。因此,本篇論文 探討 M33 透過 PcG-mediated 或是 SUV39H1 和 G9a 的參與,使異染色質形成。為 了解 M33 是否透過 PcG-mediated 的機制使異染色質形成,我 knock down PRC2 的 成員 EZH2 或 EED,發現不會降低 M33 誘導 DAPI dots 形成的能力和轉錄抑制活 性,且表現 H3K27me3 的 demethylaseJMJD3 或 UTX,亦不會減弱 M33的轉錄 抑制活性。從以上結果顯示:M33 應該不是透過 H3K27me3-mediated 的機制誘導 異染色質形成。我們推測 M33 可能藉由吸引 H3K9 的 HMT SUV39H1 或 G9a 來 幫助異染色質形成,為探討 SUV39H1 及 G9a 能否被 M33 吸引,我同時表現 M33 和 SUV39H1 或 G9a,發現 M33 能夠和 SUV39H1 和 G9a 重疊並進行交互作用, 顯示 SUV39H1 和 G9a 會被 M33 吸引。為探討 SUV39H1 和 G9a 是否參與 M33 誘導的異染色質形成,我們 knock down SUV39H1 或 G9a,發現降低 M33 誘導 DAPI dots 形成和緊縮染色質的能力,綜合以上結果顯示,M33 會吸引 SUV39H1 和 G9a 並幫助異染色質形成。研究發現 progeria 病患細胞中有 Progerin (Lamin A 突變株) 堆積,使細胞核膜不完整,且染色質結構變得鬆散,我們推測 M33 應該 能夠復原核膜不完整情形,免疫螢光染色法的結果顯示表現 M33 能夠復原 19.5 % Progerin 造成的核膜不完整,且 knock down SUV39H1 和 G9a 會降低 M33 復原核 膜不完整的比例,顯示 SUV39H1 和 G9a 能夠幫助 M33 復原核膜不完整情形。綜 合以上結果,M33 並非藉由 H3K27me3-mediated 的機制,而是透過吸引 SUV39H1 或 G9a 使異染色質形成,且此機制能夠復原 Progerin 造成的細胞核膜不完整。

Heterochromatin plays important roles in maintaining genome stability. Heterochromatin loss results in aging of the cells in progeria patients, suggesting the importance of heterochromatin formation to proper cell functions. There are two known mechanisms of heterochromatin formation. One of them is mediated by histone methyltransferase (HMT) SUV39H1 and G9a which methylate histone H3 lysine 9 (H3K9). HP1 then binds to H3K9me3 and facilitates heterochromatin formation. The other mechanism is mediated by polycomb group (PcG). PcG contains polycomb repressive complex 1 (PRC1) and PRC2. The HMT in PRC2 methylates H3K27. Chromobox (CBX) in PRC1 then binds to H3K27me3 to help heterochromatin formation. Our lab found that M33, a homolog of CBX2, induces the formation of DAPI dots which colocalize with H3K9me3 and H3K27me2 and has repressional activity, indicating that M33 has the ability to induce heterochromatin formation. Especially, only M33 in CBX family has this ability, suggesting that M33 might induce heterochromatin formation through not only PcG-mediated but also other mechanisms. It is known that M33 not only binds to H3K27me3 but also bind to H3K9me3, suggesting that M33 might induce heterochromatin formation through PcG-mediated or SUV39H1- and G9a-mediated pathway. However, the mechanism remains unknown. By knock down PRC2 components, EZH2 or EED, or removing H3K27me3 by demethylase JMJD3 or UTX, I find there is no effect on M33-induced DAPI dots formation or M33 repressional activity. The aboves show that M33 might induce heterochromatin formation through H3K27me3- independent manner. I further hypothesize that M33 might recruit SUV39H1 and G9a to help heterochromatin formation. Results of immunofluorescence and Co-IP show that M33 changes the distribution of SUV39H1 and G9a and interacts with them, indicating SUV39H1 and G9a are recruited by M33. I further knock down SUV39H1 or G9a and find deceased M33-induced DAPI dots and increased chromatin accessibility. The above shows that M33 recruits SUV39H1 and G9a to help heterochromatin formation. Heterochromatin loss and nuclear envelope disruption through Progerin, Lamin A mutant, accumulation are major phenotypes in progeria patient cells. I hypothesize M33 possess potential ability to rescue progeria. Overexpression of M33 rescues nuclear envelope disruption caused by Progerin about 19.5%. Furthermore, knock down of SUV39H1 and G9a reduces the ability of M33 to rescue nuclear envelope disruption, suggesting that M33 induces heterochromatin formation through SUV39H1 and G9a to rescue the nuclear envelope disruption. Conclusively, M33 induces heterochromatin formation through recruiting SUV39H1 and G9a, not through H3K27me3-dependent manner. M33 can rescue the envelope disruption caused by Progerin accumulation.

壹、緒論........................................................................................................................... 1 一、前言 ............................................................................................................... 1 二、真核生物的染色質 ....................................................................................... 1
(一) 染色質的組成與結構................................................................................1 (二) 異染色質形成的重要性............................................................................2 (三) 組蛋白氨基端的後轉譯修飾調控染色質結構........................................2
三、異染色質的形成機制 ................................................................................... 4 (一) SUV39H1 和 G9a 調控的異染色質形成 .................................................. 4 (二) PcG 調控的異染色質形成 ......................................................................... 5
四、M33 的背景介紹........................................................................................... 8 (一) M33 的分子結構及功能 ............................................................................ 8 (二) M33 參與的生理功能 ................................................................................ 9 (三) M33 調控基因轉錄 .................................................................................... 9 (四) M33 參與異染色質調控 .......................................................................... 10 (五) M33 在生理功能及疾病上的潛力 .......................................................... 11
五、研究目的 ..................................................................................................... 12 六、研究策略 ..................................................................................................... 13 (ㄧ) 探討 M33 是否透過 PcG-mediated 的方式形成異染色質...............13
(二) 探討 SUV39H1 或 G9a 是否被 M33 nuclear bodies 吸引,進而幫助 異染色質形成................................................................................................... 13 (三) 探討 SUV39H1 或 G9a 是否參與 M33 誘導的異染色質形成.......14 (四) 探討 M33 能否透過 SUV39H1 和 G9a 幫助復原 Progerin 堆積造 成的細胞核膜不完整情形............................................................................... 14
貳、材料與方法............................................................................................................. 15 一、質體構築 (Plasmid Construction) .............................................................. 15 (一) 本篇論文構築之質體..............................................................................15 (二) 其他質體..................................................................................................15 二、細胞培養 (CellCulture) 與基因轉移感染 (Transfection)......................15 (一) 細胞培養 (CellCulture)..........................................................................15 (二) 基因轉移感染 (Transfection).................................................................16 三、免疫螢光染色法 (Immunofluorescence)...................................................16 四、免疫共同沈澱法 (Co-Immunoprecipitation).............................................17
五、膠體電泳法 (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis) 及西方墨點法 (Western blot)................................................ 17
(一) 膠體電泳法膠體電泳法(Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis) ................................................................................................ 17 (二) 西方墨點法 (Western blot)..................................................................... 17
六、報導基因轉錄活性檢測 (Dual-Luciferase Reporter Assay).....................18 七、微球菌核酸酶剪切法 (Micrococcal Nuclease digestion Assay, MNase digestion assay).................................................................................................... 19
參、結果......................................................................................................................... 20 一、M33 不是透過已知的 PcG 機制誘導異染色質形成................................ 20 (一) PRC2 成員 EZH2 或 EED 不會降低 M33 誘導 DAPI dots 形成 .... 20 (二)PRC2成員EZH2和EED 不會減弱 M33 的轉錄抑制活性..............20 (三) 表現 JMJD3 或 UTX 皆不會減弱 M33 的轉錄抑制活性...............21 二、SUV39H1 和 G9a 會被吸引至 M33 nuclear bodies..................................21 (一) M33 能夠與 SUV39H1 和 G9a 重疊,並且有交互作用.......................21 (二) M33I17F 依然能夠與 SUV39H1 和 G9a 重疊,並且有交互作用 ....... 21 三、SUV39H1 和 G9a 參與 M33 誘導的異染色質形成 ................................. 22 (一) Knock down SUV39H1 和 G9a 降低 M33 誘導的 DAPI dots 形成 ...... 22 (二) Knock down SUV39H1 和 G9a 減弱 M33 的轉錄抑制活性 ................. 22 (三) Knock down SUV39H1 和 G9a 明顯抑制 M33 緊縮染色質的能力 .... 23 四、M33 透過SUV39H1和G9a幫助復原 Progerin 引起的核膜不完整..23 (一)M33 能夠回復因 Progerin 引起的細胞核膜不完整情形....................23 (二) Knock down SUV39H1 和 G9a 降低 M33 復原細胞核膜不完整能力 24 肆、討論......................................................................................................................... 25 一、M33 形成異染色質的機制......................................................................... 25 (一) M33 與 PcG-mediated 異染色質形成 ..................................................... 25 (二) M33 與 HMT SUV39H1 和 G9a 的關係.................................................25 二、M33 與染色質的關係................................................................................. 27 (一) M33 結合至染色質 .................................................................................. 27 (二) M33 改變染色質結構 .............................................................................. 28 三、M33 透過 SUV39H1 和 G9a 幫助復原細胞核膜不完整 ......................... 28 四、M33 的轉錄調控可能是 cell cycle-dependent........................................... 29 五、M33 在老鼠細胞中的功能......................................................................... 29 伍、參考文獻................................................................................................................. 31 陸、圖表......................................................................................................................... 40 圖一、Knock down EZH2 不會降低 M33 誘導的 DAPI dots 形成 ................ 40 圖二、Knock down EED 不會降低 M33 誘導的 DAPI dots 形成 .................. 41 圖三、Knock down EZH2 不會減弱 M33 的轉錄抑制活性 ........................... 42 圖四、Knock down EED 不會減弱 M33 的轉錄抑制活性 ............................. 43
圖五、大量表現 JMJD3 或是 UTX 不會減弱 M33 的轉錄抑制活性............44 圖六、 SUV39H1和G9a會被M33吸引.......................................................46 圖七、SUV39H1 和 G9a 可以和 M33 進行交互作用 ..................................... 47 圖八、M33I17F 仍與 SUV39H1 和 G9a 進行交互作用 ................................. 49 圖九、SUV39H1 和 G9a 依然能夠被 M33I17F 吸引 ..................................... 51 圖十、Knock down SUV39H1 或 G9a 不會降低 M33 誘導 DAPI dots 形成, 同時 knock down SUV39H1 和 G9a 使 M33 誘導 DAPI dots 減少 20 % ....... 53 圖十一、Knock down SUV39H1 和 G9a 會減弱 M33 的轉錄抑制活性........ 54 圖十二、Knock down SUV39H1 和 G9a 會抑制 M33 緊縮染色質的能力.... 55 圖十三、M33 能夠回復 19.5 % 因 Progerin 引起的細胞核膜不完整情...57 圖十四、Knock down SUV39H1 和 G9a 抑制 M33 復原核膜不完整能力...59
柒、附圖......................................................................................................................... 60

Agherbi, H., Gaussmann-Wenger, A., Verthuy, C., Chasson, L., Serrano, M., and Djabali, M. (2009). Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence. PLoS One 4, e5622.
Aoki, R., Chiba, T., Miyagi, S., Negishi, M., Konuma, T., Taniguchi, H., Ogawa, M., Yokosuka, O., and Iwama, A. (2010). The polycomb group gene product Ezh2 regulates proliferation and differentiation of murine hepatic stem/progenitor cells. J Hepatol 52, 854-863.
Babu, A., and Verma, R.S. (1986). Expression of heterochromatin by restriction endonuclease treatment and distamycin A/DAPI staining of Indian muntjac (Muntiacus muntjak) chromosomes. Cytogenet Cell Genet 41, 96-100.
Baumann, C., and De La Fuente, R. (2011). Role of polycomb group protein cbx2/m33 in meiosis onset and maintenance of chromosome stability in the Mammalian germline. Genes (Basel) 2, 59-80.
Bednar, J., Horowitz, R.A., Grigoryev, S.A., Carruthers, L.M., Hansen, J.C., Koster, A.J., and Woodcock, C.L. (1998). Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proc Natl Acad Sci U S A 95, 14173-14178.
Benitz, S., Regel, I., Reinhard, T., Popp, A., Schaffer, I., Raulefs, S., Kong, B., Esposito, I., Michalski, C.W., and Kleeff, J. (2016). Polycomb repressor complex 1 promotes gene silencing through H2AK119 mono-ubiquitination in acinar-to-ductal metaplasia and pancreatic cancer cells. Oncotarget 7, 11424-11433.
Bernstein, E., Duncan, E.M., Masui, O., Gil, J., Heard, E., and Allis, C.D. (2006). Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Mol Cell Biol 26, 2560-2569.
Boros, J., Arnoult, N., Stroobant, V., Collet, J.F., and Decottignies, A. (2014). Polycomb repressive complex 2 and H3K27me3 cooperate with H3K9 methylation to maintain heterochromatin protein 1alpha at chromatin. Mol Cell Biol 34, 3662-3674.
Bracken, A.P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard-Monch, K., Minucci, S., Porse, B.T., Marine, J.C., et al. (2007). The
Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 21, 525-530.
Brasher, S.V., Smith, B.O., Fogh, R.H., Nietlispach, D., Thiru, A., Nielsen, P.R., Broadhurst, R.W., Ball, L.J., Murzina, N.V., and Laue, E.D. (2000). The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J 19, 1587-1597.
Buratowski, S., and Kim, T. (2010). The role of cotranscriptional histone methylations. Cold Spring Harb Symp Quant Biol 75, 95-102.
Camerini-Otero, R.D., and Felsenfeld, G. (1977). Histone H3 disulfide dimers and nucleosome structure. Proc Natl Acad Sci U S A 74, 5519-5523.
Cao, R., and Zhang, Y. (2004). SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol Cell 15, 57-67.
Caretti, G., Di Padova, M., Micales, B., Lyons, G.E., and Sartorelli, V. (2004). The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev 18, 2627-2638.
Carruthers, L.M., Bednar, J., Woodcock, C.L., and Hansen, J.C. (1998). Linker histones stabilize the intrinsic salt-dependent folding of nucleosomal arrays: mechanistic ramifications for higher-order chromatin folding. Biochemistry 37, 14776-14787.
Chen, Z.-J., Wang, W.-P., Chen, Y.-C., Wang, J.-Y., Lin, W.-H., Tai, L.-A., Liou, G.-G., Yang, C.-S., and Chi, Y.-H. (2014). Dysregulated interactions between lamin A and SUN1 induce abnormalities in the nuclear envelope and endoplasmic reticulum in progeric laminopathies. J Cell Sci 127, 1792-1804.
Christen, B., and Bienz, M. (1994). Imaginal disc silencers from Ultrabithorax: evidence for Polycomb response elements. Mech Dev 48, 255-266.
Cleard, F., Delattre, M., and Spierer, P. (1997). SU(VAR)3-7, a Drosophila heterochromatin-associated protein and companion of HP1 in the genomic silencing of position-effect variegation. EMBO J 16, 5280-5288.
Clermont, P.L., Crea, F., Chiang, Y.T., Lin, D., Zhang, A., Wang, J.Z., Parolia, A., Wu, R., Xue, H., Wang, Y., et al. (2016). Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer. Clin Epigenetics 8, 16.
Columbaro, M., Capanni, C., Mattioli, E., Novelli, G., Parnaik, V.K., Squarzoni, S., Maraldi, N.M., and Lattanzi, G. (2005). Rescue of heterochromatin organization in Hutchinson-Gilford progeria by drug treatment. Cell Mol Life Sci 62, 2669-2678.
Core, N., Bel, S., Gaunt, S.J., Aurrand-Lions, M., Pearce, J., Fisher, A., and Djabali, M. (1997). Altered cellular proliferation and mesoderm patterning in Polycomb-M33- deficient mice. Development 124, 721-729.
Cuperlovic-Culf, M., Touaibia, M., St-Coeur, P.D., Poitras, J., Morin, P., and Culf, A.S. (2014). Metabolic Effects of Known and Novel HDAC and SIRT Inhibitors in Glioblastomas Independently or Combined with Temozolomide. Metabolites 4, 807-830.
Davies, N., and Lindsey, G.G. (1991). Histone-DNA contacts in the 167 bp 2-turn core particle. Biochim Biophys Acta 1129, 57-63.
de la Cruz, C.C., Kirmizis, A., Simon, M.D., Isono, K., Koseki, H., and Panning, B. (2007). The polycomb group protein SUZ12 regulates histone H3 lysine 9 methylation and HP1 alpha distribution. Chromosome Res 15, 299-314.
Endoh, M., Endo, T.A., Endoh, T., Fujimura, Y., Ohara, O., Toyoda, T., Otte, A.P., Okano, M., Brockdorff, N., Vidal, M., et al. (2008). Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity. Development 135, 1513-1524.
Eskeland, R., Leeb, M., Grimes, G.R., Kress, C., Boyle, S., Sproul, D., Gilbert, N., Fan, Y., Skoultchi, A.I., Wutz, A., et al. (2010). Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol Cell 38, 452-464.
Fenley, A.T., Adams, D.A., and Onufriev, A.V. (2010). Charge state of the globular histone core controls stability of the nucleosome. Biophys J 99, 1577-1585.
Fischle, W., Dequiedt, F., Fillion, M., Hendzel, M.J., Voelter, W., and Verdin, E. (2001). Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo. J Biol Chem 276, 35826-35835.
Gangaraju, V.K., and Bartholomew, B. (2007). Mechanisms of ATP dependent chromatin remodeling. Mutat Res 618, 3-17.
Gecz, J., Pollard, H., Consalez, G., Villard, L., Stayton, C., Millasseau, P., Khrestchatisky, M., and Fontes, M. (1994). Cloning and expression of the murine homologue of a putative
human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3. Hum Mol Genet 3, 39-44.
Grunstein, M. (1997). Histone acetylation in chromatin structure and transcription. Nature 389, 349-352.
Gupta-Agarwal, S., Franklin, A.V., Deramus, T., Wheelock, M., Davis, R.L., McMahon, L.L., and Lubin, F.D. (2012). G9a/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation. J Neurosci 32, 5440-5453.
Haldar, S., Saini, A., Nanda, J.S., Saini, S., and Singh, J. (2011). Role of Swi6/HP1 self- association-mediated recruitment of Clr4/Suv39 in establishment and maintenance of heterochromatin in fission yeast. J Biol Chem 286, 9308-9320.
Hatano, A., Matsumoto, M., Higashinakagawa, T., and Nakayama, K.I. (2010). Phosphorylation of the chromodomain changes the binding specificity of Cbx2 for methylated histone H3. Biochem Biophys Res Commun 397, 93-99.
Hirose, S., Komoike, Y., and Higashinakagawa, T. (2006). Identification of a nuclear localization signal in mouse polycomb protein, M33. Zoolog Sci 23, 785-791.
Hublitz, P., Albert, M., and Peters, A.H. (2009). Mechanisms of transcriptional repression by histone lysine methylation. Int J Dev Biol 53, 335-354.
Imai, K., Kamio, N., Cueno, M.E., Saito, Y., Inoue, H., Saito, I., and Ochiai, K. (2014). Role of the histone H3 lysine 9 methyltransferase Suv39 h1 in maintaining Epsteinn-Barr virus latency in B95-8 cells. FEBS J 281, 2148-2158.
Ismail, I.H., Andrin, C., McDonald, D., and Hendzel, M.J. (2010). BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair. J Cell Biol 191, 45-60.
Isono, K., Endo, T.A., Ku, M., Yamada, D., Suzuki, R., Sharif, J., Ishikura, T., Toyoda, T., Bernstein, B.E., and Koseki, H. (2013). SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing. Dev Cell 26, 565-577.
Ito, T. (2007). Role of histone modification in chromatin dynamics. J Biochem 141, 609- 614.
Kalantry, S., Mills, K.C., Yee, D., Otte, A.P., Panning, B., and Magnuson, T. (2006). The Polycomb group protein Eed protects the inactive X-chromosome from differentiation- induced reactivation. Nat Cell Biol 8, 195-202.
Kao, H.Y., Lee, C.H., Komarov, A., Han, C.C., and Evans, R.M. (2002). Isolation and characterization of mammalian HDAC10, a novel histone deacetylase. J Biol Chem 277, 187-193.
Kapuscinski, J. (2009). DAPI: a DNA-specific fluorescent probe. Biotechnic & Histochemistry 7, 220-233.
Katoh-Fukui, Y., Owaki, A., Toyama, Y., Kusaka, M., Shinohara, Y., Maekawa, M., Toshimori, K., and Morohashi, K. (2005). Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression. Blood 106, 1612-1620.
Kimura, A., and Horikoshi, M. (1998). How do histone acetyltransferases select lysine residues in core histones? FEBS Lett 431, 131-133.
Kingston, R.E., Bunker, C.A., and Imbalzano, A.N. (1996). Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev 10, 905-920.
Ku, M., Koche, R.P., Rheinbay, E., Mendenhall, E.M., Endoh, M., Mikkelsen, T.S., Presser, A., Nusbaum, C., Xie, X., Chi, A.S., et al. (2008). Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet 4, e1000242.
Kundu, S., and Peterson, C.L. (2009). Role of chromatin states in transcriptional memory. Biochim Biophys Acta 1790, 445-455.
Kundu, S., Horn, P.J., and Peterson, C.L. (2007). SWI/SNF is required for transcriptional memory at the yeast GAL gene cluster. Genes Dev 21, 997-1004.
Kuzmichev, A., Margueron, R., Vaquero, A., Preissner, T.S., Scher, M., Kirmizis, A., Ouyang, X., Brockdorff, N., Abate-Shen, C., Farnham, P., et al. (2005). Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Proc Natl Acad Sci U S A 102, 1859-1864.
Li, X., Yang, F., Chen, H., Deng, B., Li, X., and Xi, R. (2016). Control of germline stem cell differentiation by polycomb and trithorax group genes in the niche microenvironment. Development.
Lin, S.S., Martin, R., Mongrand, S., Vandenabeele, S., Chen, K.C., Jang, I.C., and Chua, N.H. (2008). RING1 E3 ligase localizes to plasma membrane lipid rafts to trigger FB1- induced programmed cell death in Arabidopsis. Plant J 56, 550-561.
Liu, B., Wang, Z., Zhang, L., Ghosh, S., Zheng, H., and Zhou, Z. (2013). Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nat Commun 4, 1868.
McGhee, J.D., and Felsenfeld, G. (1980). The number of charge-charge interactions stabilizing the ends of nucleosome DNA. Nucleic Acids Res 8, 2751-2769.
Meselson, M. (1979). Chromatin structure and histone modification. Differentiation 13, 41-42.
Montgomery, N.D., Yee, D., Montgomery, S.A., and Magnuson, T. (2007). Molecular and functional mapping of EED motifs required for PRC2-dependent histone methylation. J Mol Biol 374, 1145-1157.
Mozzetta, C., Pontis, J., Fritsch, L., Robin, P., Portoso, M., Proux, C., Margueron, R., and Ait-Si-Ali, S. (2014). The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing. Mol Cell 53, 277-289.
Muller, C., and Leutz, A. (2001). Chromatin remodeling in development and differentiation. Curr Opin Genet Dev 11, 167-174.
Muramatsu, D., Singh, P.B., Kimura, H., Tachibana, M., and Shinkai, Y. (2016). Pericentric heterochromatin generated by HP1 protein interaction-defective histone methyltransferase Suv39h1. J Biol Chem 291, 14393.
Nielsen, A.L., Oulad-Abdelghani, M., Ortiz, J.A., Remboutsika, E., Chambon, P., and Losson, R. (2001). Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol Cell 7, 729-739.
Ozawa, Y., Towatari, M., Tsuzuki, S., Hayakawa, F., Maeda, T., Miyata, Y., Tanimoto, M., and Saito, H. (2001). Histone deacetylase 3 associates with and represses the transcription factor GATA-2. Blood 98, 2116-2123.
Papp, B., and Muller, J. (2006). Histone trimethylation and the maintenance of transcriptional ON and OFF states by trxG and PcG proteins. Genes Dev 20, 2041-2054.
Paro, R., and Hogness, D.S. (1991). The Polycomb protein shares a homologous domain with a heterochromatin-associated protein of Drosophila. Proc Natl Acad Sci U S A 88, 263-267.
Pasini, D., Bracken, A.P., Hansen, J.B., Capillo, M., and Helin, K. (2007). The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol 27, 3769-3779.
Pasini, D., Bracken, A.P., Jensen, M.R., Lazzerini Denchi, E., and Helin, K. (2004). Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J 23, 4061-4071.
Pearce, J.J., Singh, P.B., and Gaunt, S.J. (1992). The mouse has a Polycomb-like chromobox gene. Development 114, 921-929.
Peters, A.H., O''Carroll, D., Scherthan, H., Mechtler, K., Sauer, S., Schofer, C., Weipoltshammer, K., Pagani, M., Lachner, M., Kohlmaier, A., et al. (2001). Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107, 323-337.
Pinheiro, I., Margueron, R., Shukeir, N., Eisold, M., Fritzsch, C., Richter, F.M., Mittler, G., Genoud, C., Goyama, S., Kurokawa, M., et al. (2012). Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150, 948-960.
Postepska-Igielska, A., Krunic, D., Schmitt, N., Greulich-Bode, K.M., Boukamp, P., and Grummt, I. (2013). The chromatin remodelling complex NoRC safeguards genome stability by heterochromatin formation at telomeres and centromeres. EMBO Rep 14, 704-710.
Rodriguez, J., Mosquera, J., Couceiro, J.R., Vazquez, M.E., and Mascarenas, J.L. (2015). The AT-Hook motif as a versatile minor groove anchor for promoting DNA binding of transcription factor fragments. Chem Sci 6, 4767-4771.
Ryan, R.F., Schultz, D.C., Ayyanathan, K., Singh, P.B., Friedman, J.R., Fredericks, W.J., and Rauscher, F.J., 3rd (1999). KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Kruppel-associated box-zinc finger proteins in heterochromatin-mediated gene silencing. Mol Cell Biol 19, 4366-4378.
Shinkai, Y., and Tachibana, M. (2011). H3K9 methyltransferase G9a and the related molecule GLP. Genes Dev 25, 781-788.
Simon, J.A., and Kingston, R.E. (2009). Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 10, 697-708.
Souza, P.P., Volkel, P., Trinel, D., Vandamme, J., Rosnoblet, C., Heliot, L., and Angrand, P.O. (2009). The histone methyltransferase SUV420H2 and Heterochromatin Proteins HP1 interact but show different dynamic behaviours. BMC Cell Biol 10, 41.
Svaren, J., and Horz, W. (1996). Regulation of gene expression by nucleosomes. Curr Opin Genet Dev 6, 164-170.
Tachibana, M., Ueda, J., Fukuda, M., Takeda, N., Ohta, T., Iwanari, H., Sakihama, T., Kodama, T., Hamakubo, T., and Shinkai, Y. (2005). Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev 19, 815-826.
Tardat, M., Albert, M., Kunzmann, R., Liu, Z., Kaustov, L., Thierry, R., Duan, S., Brykczynska, U., Arrowsmith, C.H., and Peters, A.H. (2015). Cbx2 targets PRC1 to constitutive heterochromatin in mouse zygotes in a parent-of-origin-dependent manner. Mol Cell 58, 157-171.
Trievel, R.C., Beach, B.M., Dirk, L.M., Houtz, R.L., and Hurley, J.H. (2002). Structure and catalytic mechanism of a SET domain protein methyltransferase. Cell 111, 91-103.
van den Boom, V., Rozenveld-Geugien, M., Bonardi, F., Malanga, D., van Gosliga, D., Heijink, A.M., Viglietto, G., Morrone, G., Fusetti, F., Vellenga, E., et al. (2013). Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cells. Blood 121, 2452-2461.
van der Vlag, J., and Otte, A.P. (1999). Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet 23, 474-478.
Yamamoto, K., and Sonoda, M. (2003). Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1. Biochem Biophys Res Commun 301, 287-292.
Yamamoto, M.T., Mitchelson, A., Tudor, M., O''Hare, K., Davies, J.A., and Miklos, G.L. (1990). Molecular and cytogenetic analysis of the heterochromatin-euchromatin junction region of the Drosophila melanogaster X chromosome using cloned DNA sequences. Genetics 125, 821-832.
Zhen, C.Y., Duc, H.N., Kokotovic, M., Phiel, C.J., and Ren, X. (2014). Cbx2 stably associates with mitotic chromosomes via a PRC2- or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes. Mol Biol Cell 25, 3726- 3739.
Zhou, X., Marks, P.A., Rifkind, R.A., and Richon, V.M. (2001). Cloning and characterization of a histone deacetylase, HDAC9. Proc Natl Acad Sci U S A 98, 10572- 10577.

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