X染色体的DNA序列结构不同于6、7、8、10、11、12号染色体

雌性哺乳动物X染色体上的大部分基因均因X染色体失活作用而失去表达能力 ,X染色体长臂表现失活更明显。虽然对X染色体失活的许多方面都有所了解 ,但是仍然不清楚失活信号沿着X染色体全长扩散的机制。为了了解X染色体是否有不同于其他染色体的基因组学特征 ,这些特征是否关系到X染色体的失活扩散和维持 ,分析 6、7、8、1 0、1 1、1 2号染色体和X染色体DNA序列 7碱基 (7nt)组合水平的结构是否显示差异。从NCBI基因库(http :∥www .ncbi.nlm .nih .gov genome guide)下载 7条染色体长臂各 6 0Mb区域。将这 6 0Mb区域分为 0 5Mb (或 5 0kb)一段 ,对每一段DNA做 7nt字符串组合分析 ,如 1～ 7,2～ 8,3～ 9…… ,记录每种 7nt字符串的频率 ,A、C、G和T4个硷基的 7nt字符串共有 4 7=1 6 384种组合。根据数字差异显示的结果 (http :∥www .ncbi.nlm .nih .gov genome guide) ,选择在扁桃腺生发中心B细胞中高表达的基因 70个 ,用以计算所有内含子 (有义链 )的 7nt频率值。每个内含子被记录为一组 7nt频率值 ,求和相同基因中的所有内含子相同 7nt字符串的频率值 ,再用该和乘以该基因的表达频率得该基因 7nt字符串的频率值 ,求和 70个基因的 7nt字符串的频率值称做intron 7nt,该值试图模拟细胞中RNA小片段的总和。

DNA Sequence Composition on Human X Chromosome Differing from that on Chromosomes 6,7,8,10,11 and 12

To test whether X chromosome has unique genomic characteristics involved in the propagation and maintenance of X chromosome inactivation,X chromosome and autosomes (chromosomes 6,7,8,10,11 and 12) were compared for frequencies of 7-nucleotide strings（7 nt）.60 Mb nucleotide sequences on long arms of 7 chromosomes were divided into 120 (or 1200) segments of 0.5 Mb (or 50 kb) per segment that was recoded as a set of frequency values of 7-nucleotide strings using all possible 7-nucleotide strings (47=16384).70 genes highly expressed in tonsil germinal center B cells were selected for calculating 7 nt frequency values of all introns (intron 7 nt).The binding density of DNA segment and intron 7 nt simulates the sum of binding density of the DNA segment to RNA fragments.It is found that chromosomes X,6 and 8 are more uniform in terms of different 0.5 Mb segments.The simulative binding density to RNAs is significantly lower on X chromosome than on chromosomes 6,7,8 and 12 (P＜0.001).The segments that can highly bind RNAs are less on X than those on others,although no significant difference was found in comparison with chromosomes 6 and 11 when 0.5 Mb DNA was considered as a segment.But when 50 kb DNA was considered as a segment,the DNA segments highly binding RNAs on X chromosome were significantly less than those on chromosomes 6 and 11 (P＜0.001).The data presented in this paper indicate that the DNA sequence composition of the human X chromosome is fundamentally distinct from that of human autosomes analyzed.This nonrandom property of distribution of RNA highly binding segments between the X chromosome and autosomes provides strong evidence that RNA highly binding segments may serve as DNA signals to propagate activation along a chromosome.It has been proved that RNAs alter chromatin structure and increase its sensitivity to DNaseⅠ.There is plenty of nonprotein-coding RNA in cells,the binding specificity of DNA-RNA is far higher than that of DNA-protein,and the affinity of DNA with RNA is higher as compared with DNA.These facts indicate that the interaction of RNA-DNA in cells may be extensive.The important finding in this study is that the binding ability to RNAs,especially the number of DNA segments highly binding RNAs is significantly lower on X chromosome than on other chromosomes.These facts suggest that if binding of DNA segment to RNAs opens the chromatin,it is easier for DNA segments on X chromosome to become heterochromatin because the numbers of DNA segments highly binding RNAs are significantly less on X chromosome than on others.It is proposed that the mechanism of X inactivation perhaps is due to lack of RNA activation during DNA replication,and early in female development in eutherian mammals lack of activators in cells could result in competition for access to them between 2 X chromosomes,which may be a cause of X chromosome inactivation.In cell cycle the quality and quantity of RNAs change continuously,so the RNAs (summation of RNA small fragments in cells) contacted by early replicating DNA are different from those by later replicating DNA.Early replicating DNA has opportunity to bind more RNAs and maintains sufficiently active state,and vice versa,which may be the reason why the states of the active and inactive X chromosomes could be maintained in somatic cells.