Birchler James A, Pal-Bhadra Manika, Bhadra Utpal
University of Missouri, Columbia, 117 Tucker Hall, Columbia, MO 65211-7400, USA.
Genetica. 2003 Mar;117(2-3):179-90. doi: 10.1023/a:1022935927763.
Dosage compensation refers to the phenomenon that despite the difference in copy number of X chromosomes in males and females approximately equal expression results from the sex chromosomes. We describe evidence for a model that dosage compensation is caused by an 'inverse dosage effect' that results from an altered stoichiometry of transcriptional regulators on the X versus the autosomes. This imbalance of regulators would cause a two-fold increase in target gene expression throughout the genome in the absence of any modification. The two-fold hyperactivation compensates the X chromosome. However, the MSL (male specific lethal) complex modifies this effect on the autosomes, which would otherwise double their expression, by becoming sequestered to the X chromosome together with a histone acetylase (MOF) and kinase (JIL1). This situation reduces the level of histone 4 Lys16 acetylation and H3 phosphorylation on the autosomes, thus bringing their expression down to near the female level. The presence of the MSL complex on the X modifies chromatin in such a manner that it counteracts any impact of increased histone acetylation and phosphorylation on gene expression. This situation fosters the proper two-fold increase in gene expression needed for X chromosomal dosage compensation in males and reduces the inverse effect on the autosomes to equalize gene expression throughout the genome for the two sexes.
剂量补偿是指尽管雄性和雌性X染色体的拷贝数存在差异，但性染色体的表达结果大致相等的现象。我们描述了一个模型的证据，即剂量补偿是由一种“反向剂量效应”引起的，这种效应是由于X染色体与常染色体上转录调节因子的化学计量改变所致。在没有任何修饰的情况下，这种调节因子的失衡会导致整个基因组中靶基因表达增加两倍。这种两倍的过度激活补偿了X染色体。然而，MSL（雄性特异性致死）复合体通过与组蛋白乙酰转移酶（MOF）和激酶（JIL1）一起被隔离到X染色体上，从而改变了对常染色体的这种效应，否则常染色体的表达会加倍。这种情况降低了常染色体上组蛋白4赖氨酸16乙酰化和H3磷酸化的水平，从而使其表达降至接近雌性水平。X染色体上MSL复合体的存在以这样一种方式修饰染色质，即它抵消了组蛋白乙酰化和磷酸化增加对基因表达的任何影响。这种情况促进了雄性X染色体剂量补偿所需的基因表达适当增加两倍，并减少了对常染色体的反向效应，以使两性整个基因组的基因表达达到平衡。
