分子遺傳學(xué)2013-1課件

1、遺傳與細(xì)胞研究所 陸 軍表觀遺傳修飾與乳腺癌轉(zhuǎn)移 2013年遺傳與細(xì)胞學(xué)科群學(xué)術(shù)交流與研討會表觀遺傳修飾與基因表達(dá)調(diào)控研究方向表觀遺傳修飾與乳腺癌轉(zhuǎn)移1表觀遺傳修飾與細(xì)胞及個體衰老 2研究方向乳腺癌-高發(fā)區(qū)：所有城市 上皮中的腫瘤基底膜破壞基底膜侵入血管血管隨著血液流動黏附于血管壁腫瘤侵入上皮形成新的轉(zhuǎn)移灶腫瘤轉(zhuǎn)移模型表觀遺傳修飾與癌癥遺傳學(xué)與表觀遺傳學(xué)遺傳學(xué)：DNA模板的突變能夠通過生殖細(xì)胞遺傳。表觀遺傳學(xué)：通過DNA甲基化，組蛋白修飾，染色質(zhì)重塑，非編碼RNA等方式引發(fā)的染色質(zhì)結(jié)構(gòu)的改變來調(diào)節(jié)基因的功能。染色質(zhì)上的這些標(biāo)記在細(xì)胞分裂過程中被遺傳并共同決定細(xì)胞的表型。組蛋白修飾與基因轉(zhuǎn)錄Ta

2、rakhovsky A. Nature Immunology, 2010組蛋白修飾與基因轉(zhuǎn)錄IBMS BoneKEy. 2010 September;7(9):314-324.WritersEraser組蛋白修飾酶（Writer 和 Eraser）Readers組蛋白與Reader 癌癥的表觀遺傳學(xué)癌癥的表觀遺傳學(xué)癌癥進(jìn)程中的表觀遺傳學(xué)變化精氨酸甲基化修飾與乳腺癌轉(zhuǎn)移蛋白質(zhì)精氨酸甲基化是一種廣泛的翻譯后修飾方式。在RNA加工、轉(zhuǎn)錄調(diào)控、信號轉(zhuǎn)導(dǎo)、DNA修復(fù)等多種細(xì)胞過程中發(fā)揮重要作用。研究模型（EMT）研究內(nèi)容 EMT RegulatorsPRMT7 mediates epithelial t

3、o mesenchymal transition and promotes breast cancer metastasis and tumorigenesis1. PRMT7 expression is associated with malignant breast cancerBWeak+Moderate+Strong+CDETumor typeTotal no. of casesNo.with high-levelexpression for PRMT7Percentage with highPRMT7 expression (%)PEstrogen Receptor114 0.025

4、6Positive701521.4Negative441840.9Progesterone receptor114 0.099Positive621524.2Negative522038.5Histologic grade114 0.036I/II691521.7III451840Molecular type110 0.04Luminal-like701622.9Basal-like221150Her2+18738.9Table 1. Association between PRMT7 expression and clinicopathological tumor types in brea

5、st carcinomas3. PRMT7 promotes migration and invasion 4. Elevated H4R3me2s and the corresponding reduced H3K4me3 on the E-cadherin promoter occur in EMTAPRMT7H4R3me2sH3K4me3InputNo AbshCtrlshPRMT7HDAC3H3AcH4AcInputNo AbVectorPRMT7Input: HisYY1HisVectorPRMT7VectorHisNo AbPRMT7YY1 -actinYY1PRMT7PRMT7N

6、o AbInputMDA-MB-231MCF7-PRMT75. PRMT7 can promote breast cancer distant metastasisVectorPRMT75. PRMT7 can promote breast cancer distant metastasisVectorPRMT7n=8n=95. PRMT7 can promote breast cancer distant metastasis5. PRMT7 can promote breast cancer distant metastasisR3H3H4E-cadCo-repressorHDAC3 H3

7、AcH4AcH3K4me3PRMT7H4R3me2S YY1PRMT7擬開展工作VectoRMT7MarkerPRMT7KDaWDR5K.IWDVSSGK.CK.LWDYSK.GK.IWGAYDGK.FK.IWDVSSGKCLK.TR.IWDTASGQCLK.TK.TLPAHSDPVSAVHFNR.DK.CLKTLPAHSDPVSAVHFNR.DK.IWGAYDGKFEK.TK.TLKIWDVSSGK.CK.AVSSVKFSPNGEWLASSSADK.LK.TYTGHKNEKYCIFANFSVTGGK.WK.LQGHTDVVISTACHPTENIIASAALENDK.TK.LQGHTDVVISTACHPTENIIASAALENDKTIK.LK.FSPNGEWLASSSADKLIK.IR.DGSLIVSSSYDGLCR.IK.AVSSVKFSPNGEWLASSSADKLIK.IK.TLIDDDNPPVSFVK.FK.TISGHKLGISDVAWSSDSNLLVSASDDKTLK.IK.YCIFANFSVTGGK.WK.FSPNGKYILAATLDNTLK.LK.YILAATLDNTLK.LK.GHSNYVFCCNFNPQSNLIVSGSFDESVR.IK.LGISDVAWSSDSNLLVSASDDK.TR.IWDTA