Word frequency analysis reveals enrichment of dinucleotide repeats on the human X chromosome and [GATA]n in the X escape region
Word frequency analysis reveals enrichment of dinucleotide repeats on the human X chromosome and [GATA]n in the X escape region
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DOI：
10.1101/gr.4627606
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发表时间：
2006-04-01
期刊：
影响因子：
7
通讯作者：
Lawrence, JB
中科院分区：
文献类型：
--
作者：
McNeil, JA;Smith, KP;Lawrence, JB
大多数人类基因组既不编码蛋白质，也不编码已知的功能性RNA，但在“非编码”序列中寻找有意义信息的方法是有限的。X染色体的独特生物学特性（其中一条在哺乳动物雌性中是沉默的）可以为染色体包装和功能所涉及的序列基序提供线索。虽然常染色体染色质具有一定的失活能力，但有证据表明，X染色体上富集的序列使其完全有能力沉默，除了逃避失活的特定区域。在这里，我们使用了语言学的方法，通过分析整个人类基因组中九个碱基对基因组“单词”的频率和分布。结果确定了人类X染色体上以前未知的序列差异。值得注意的是，与常染色体相比，二核苷酸重复[AT]（n）、[AC]（n）和[AG]（n）在X染色体上显著富集。此外，[加塔]（n）的显著富集（> 10倍）在Xp 22的10-Mb片段中显示，其逃避失活，并通过荧光原位杂交证实。在其他真兽目基因组中也发现了类似的富集。我们的研究结果清楚地表明了与X染色体的新生物学和进化相关的序列差异。此外，他们牵连简单的序列重复，连接到基因调控和不寻常的DNA结构，在调节和形成的兼性异染色质。结果表明，一个新的范例，即区域逃避X失活是由于存在的元素，防止异染色质化，而不是缺乏其他元素，促进它。
Most of the human genome encodes neither protein nor known functional RNA, yet available approaches to seek meaningful information in the "noncoding" sequence are limited. The unique biology of the X chromosome, one of which is silenced in mammalian females, can yield clues into sequence motifs involved in chromosome packaging and function. Although autosomal chromatin has some capacity for inactivation, evidence indicates that sequences enriched on the X chromosome render it fully competent for silencing, except in specific regions that escape inactivation. Here we have used a linguistic approach by analyzing the frequency and distribution of nine base-pair genomic "words" throughout the human genome. Results identify previously unknown sequence differences on the human X chromosome. Notably, the dinucleotide repeats [AT](n), [AC](n), and [AG](n) are significantly enriched across the X chromosome compared with autosomes. Moreover, a striking enrichment (> 10-fold) of [GATA](n) is revealed throughout the 10-Mb segment at Xp22 that escapes inactivation, and is confirmed by fluorescence in situ hybridization. A similar enrichment is found in other eutherian genomes. Our findings clearly demonstrate sequence differences relevant to the novel biology and evolution of the X chromosome. Furthermore, they implicate simple sequence repeats, linked to gene regulation and unusual DNA structures, in the regulation and formation of facultative heterochromatin. Results suggest a new paradigm whereby a regional escape from X inactivation is due to the presence of elements that prevent heterochromatinization, rather than the lack of other elements that promote it.