MSL(male specific lethal)复合体作为调节果蝇剂量补偿的关键元件,在非整倍体基因表达调控过程中发挥了重要作用.为深入探究非整倍体胚胎发育过程的分子调控机制,运用TSA-FISH(tyramide signal amplificationfluorescence in situ hybr...MSL(male specific lethal)复合体作为调节果蝇剂量补偿的关键元件,在非整倍体基因表达调控过程中发挥了重要作用.为深入探究非整倍体胚胎发育过程的分子调控机制,运用TSA-FISH(tyramide signal amplificationfluorescence in situ hybridization)技术比较分析正常二倍体胚胎与常染色体三体胚胎中的MSL复合体组分基因表达模式,探究复合体重要组分在果蝇非整倍体胚胎不同时期的表达水平,以及亚细胞定位的变化.研究结果表明,在MSL复合体尚未组装的非整倍体胚胎发育早期,即母体表达阶段,多数复合体组分基因就已存在转录本水平上的差异,而这种表达差异主要源自于母体的非单倍体配子.随着发育的进行,染色体片段的增加导致基因组内剂量平衡发生变化,由此产生的反式剂量效应将引发MSL复合体各组分表达水平的差异变化,而这种差异将持续作用于后续非整倍体胚胎发育的各个时期.展开更多
Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast ca...Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere lengths by causing a significant and stable increase in telomere lengths of the breast cancer cell line. The increase in telomere lengths was consistently observed when various telomere length methods were used. Conclusions: Further investigation is required to understand the underlying mechanism involved, and the significance of telomere length elongation in relation to clinical outcome when epigenetic modifying drugs are utilized.展开更多
文摘MSL(male specific lethal)复合体作为调节果蝇剂量补偿的关键元件,在非整倍体基因表达调控过程中发挥了重要作用.为深入探究非整倍体胚胎发育过程的分子调控机制,运用TSA-FISH(tyramide signal amplificationfluorescence in situ hybridization)技术比较分析正常二倍体胚胎与常染色体三体胚胎中的MSL复合体组分基因表达模式,探究复合体重要组分在果蝇非整倍体胚胎不同时期的表达水平,以及亚细胞定位的变化.研究结果表明,在MSL复合体尚未组装的非整倍体胚胎发育早期,即母体表达阶段,多数复合体组分基因就已存在转录本水平上的差异,而这种表达差异主要源自于母体的非单倍体配子.随着发育的进行,染色体片段的增加导致基因组内剂量平衡发生变化,由此产生的反式剂量效应将引发MSL复合体各组分表达水平的差异变化,而这种差异将持续作用于后续非整倍体胚胎发育的各个时期.
文摘Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere lengths by causing a significant and stable increase in telomere lengths of the breast cancer cell line. The increase in telomere lengths was consistently observed when various telomere length methods were used. Conclusions: Further investigation is required to understand the underlying mechanism involved, and the significance of telomere length elongation in relation to clinical outcome when epigenetic modifying drugs are utilized.
