Genome wide profiling of histone variants in colorectal cancer cells

结直肠癌细胞组蛋白变异的全基因组分析

• 批准号: 7966216
• 负责人: YAMINI P DALAL
• 金额: $ 52.96万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7966216
• 关键词: Address; Area; Cancer cell line; Centromere; Chromosomal Instability; Colorectal Cancer; Epigenetic Process; Failure; Functional RNA; Genes; Genome; Goals; Histones; Invaded; Location; Maps; Methods; Microscopy; Nucleic Acid Regulatory Sequences; Outcome; Proteins; Site; Variant; cancer cell; genome-wide; new technology; single molecule

We have mapped CENPA genome wide in 4 colorectal cancer cell lines and found that instead of being broadly mis-localized as was originally hypothesized, our preliminary findings suggest that it is clustered tightly within a 1000bp windown in very specific locations. These locations appear to areas of the genome that are enriched in genes, area of the genome that contain regulatory regions,and areas of the genome that may potentially represent breakpoints in subtelomeres. Furthermore, we find that some sites of enrichment are common across two cancer cell lines that have the highest levels of misexpression of the CENPA protein, suggesting a common mechanism may underlie how CENPA invades non-centromeric locations in the genome. We intend to map these regions further using cytological and single molecule microscopy (AFM) methods.

我们已经在4种结直肠癌细胞系中绘制了CENPA全基因组图谱，发现 而不是广泛的错误定位，因为最初的假设，我们的初步 结果表明，它在1000bp的片段内紧密聚集， 地点这些位置似乎是基因组中富含基因的区域， 包含调控区域的基因组，以及基因组中可能 代表亚端粒的断裂点。此外，我们发现，一些网站的富集， 在两种具有最高水平的CENPA错误表达的癌细胞系中是常见的 蛋白质，这表明一个共同的机制可能是CENPA如何侵入非着丝粒的基础 基因组中的位置。我们打算进一步利用细胞学和单克隆抗体来绘制这些区域的地图。 分子显微镜（AFM）方法。