Global regulation of the C. elegans X chromosome

描述（由申请人提供）：SMC蛋白家族参与 染色体生物学的几个方面，包括有丝分裂染色体 凝聚和姐妹染色单体凝聚。在线虫中，C.优雅SMC 含有蛋白质的复合物也参与剂量补偿。的 X连锁基因表达的染色体范围调节过程， 使男性（IX）和女性（2X）的X转录物相等，尽管它们存在差异 X染色体剂量。蠕虫剂量补偿与 机械和有丝分裂染色体凝聚复合体表明，这两个 过程可能是机械相关的。随着许多基因的发展， 疾病和癌症与染色体异常有关，了解 蛋白质复合物的功能涉及染色体的不同方面 生物学将是我们寻找治疗和治愈这些疾病的关键 疾病虽然许多蛋白质和RNA分子参与剂量 补偿已被确定，其生化功能不好 明白破译这种蛋白质的生化功能的第一步 剂量补偿机制是确定复合物结合的位置， 如何识别X然后对所有X连锁的监管水平 基因将需要确定。基因表达水平与剂量的关系 补偿和非剂量补偿的染色体。线虫基因组 将使用DNA微阵列进行研究。然后寻找染色体结合 剂量补偿机械的位置将使用两个 技术：（i）染色质免疫沉淀（ChIP）的剂量补偿 复杂和结合的DNA和（ii）涉及体内的Dam识别（DamID） 使用Dam甲基转移酶连接到剂量补偿的DNA甲基化 proteins.

DESCRIPTION (provided by applicant): The SMC family of proteins participates in several aspects of chromosome biology, including mitotic chromosome condensation and sister chromatid cohesion. In the nematode, C. elegans. SMC protein containing complexes are also involved in dosage compensation. The process of chromosome-wide modulation of X-linked gene expression that equalizes X transcripts in males (IX) and females (2X) despite their difference in X chromosome dose. The similarity between the worm dosage compensation machinery and mitotic chromosome condensation complexes indicate that the two processes may be mechanistically related. As the development of many genetic diseases and cancers correlate with chromosomal abnormalities, understanding the function of protein complexes involved in different aspects of chromosome biology wilt be crucial in our search for treatments and cures for these diseases. Although many of the protein and RNA molecules involved in dosage compensation have been identified, their biochemical function is not well understood. The first step toward deciphering the biochemical function of the dosage compensation machinery is to determine where the complex binds and thus how the X is recognized. Then the level of regulation imposed on all X-linked genes will need to be determined. Expression levels of genes on dosage compensated and non-dosage compensated chromosomes in the C. elegans genome will be studied using DNA microarrays. Then a search for chromosomal binding sites of the dosage compensation machinery will be performed using two techniques: (i) chromatin immunoprecipitation (ChIP) of the dosage compensation complex and bound DNA and (ii) Dam identification (DamID) involving in viva methylation of DNA using Dam methyltransferase tethered to dosage compensation proteins.