Gene expression analysis of the function of the male-specific lethal complex in drosophila

Gene expression analysis of the function of the male-specific lethal complex in drosophila
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DOI:
10.1534/genetics.104.036020
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发表时间:
2005-04-01
期刊:
影响因子:
3.3
通讯作者:
Birchler, JA
Birchler, JA
中科院分区:
生物学2区
文献类型:
--
作者:
Bhadra, MP;Bhadra, U;Birchler, JA

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剂量补偿是指尽管两性之间的拷贝数存在差异,但X连锁基因的表达相同。配偶特异性致死(MSL)复合体集中在男性的X染色体上。胚胎的基因表达测定被开发来检查该复合物的功能。在没有MSL复合物或MOF历史乙酰化酶的突变雄性胚胎中,剂量补偿被保留,但常染色体表达增加。剂量补偿在双突变胚胎中丢失。在MSL复合物和MOF靶向雌性X染色体的胚胎中,结果与先前的调查一致,表明一般来说X表达保持不变,但常染色体表达减少。ISWI染色质重塑成分的突变导致男性X连锁基因特异性增加。因此,MSL复合物与ISWI结合的功能被假定为覆盖雄性X染色体上高组蛋白乙酰化对基因表达的影响。剂量补偿的基本决定因素被认为是由X与常染色体上的转录因子的不平衡产生的逆剂量效应。MSL复合物对男性X的隔离可能已经进化为抵消对常染色体的类似作用,并防止男性中X染色体的过度表达,否则由于高水平的组蛋白乙酰化而发生。
Dosage compensation refers to the equal expression of X-linked genes despite the difference in copy number between the two sexes. The mate-specific lethal (MSL) complex is concentrated on the X chromosome in males. A gene expression assay for embryos was developed to examine the function of this complex. In mutant male embryos without either the MSL complex or MOF historic acetylase, dosage compensation is retained but autosomal expression is increased. Dosage compensation is lost in the double-mutant embryos. In embryos in which the MSL complex and MOF are targeted to the X chromosomes in females, the results are consistent with previous surveys showing that in general the X expression remains unchanged, but autosomal expression is reduced. Mutations in the ISWI chromatin-remodeling component cause increases specifically of X-linked genes in males. Thus, the function of the MSL complex in conjunction with ISWI is postulated to override the effect on gene expression of high histone acetylation on the male X. The basic determinant of dosage compensation is suggested to be an inverse dosage effect produced by an imbalance of transcription factors on the X vs. the autosomes. The sequestration of the MSL complex to the male X may have evolved to counteract a similar effect on the autosomes and to prevent an overexpression of the X chromosome in males that would otherwise occur due to the high levels of histone acetylation.