ACETYLATED HISTONE H4 ON THE MALE X-CHROMOSOME IS ASSOCIATED WITH DOSAGE COMPENSATION IN DROSOPHILA
ACETYLATED HISTONE H4 ON THE MALE X-CHROMOSOME IS ASSOCIATED WITH DOSAGE COMPENSATION IN DROSOPHILA
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DOI：
10.1101/gad.8.1.96
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发表时间：
1994-01-01
影响因子：
10.5
通讯作者：
KURODA, MI
中科院分区：
文献类型：
--
作者：
BONE, JR;LAVENDER, J;KURODA, MI
果蝇中的剂量补偿是通过雄性 X 染色体上基因转录的增加而发生的。这种升高的表达需要至少四个位点的功能，这些位点统称为雄性特异性致死（msl）基因。其中两个基因（maleless (mle) 和雄性特异性 lethal-1 (msl-1)）编码的蛋白质与雄性 X 染色体相关，表明它们充当剂量补偿的正调节因子。组蛋白 H4 的一种特定乙酰化异构体 H4Ac16 也主要在男性 X 染色体上检测到。我们发现MLE和MSL-1以相同的模式与X染色体结合，并且X上H4Ac16的模式与MLE/MSL-1的模式很大程度上一致。我们未能在纯合 msl 男性的 X 染色体上检测到 H4Ac16，这与这些突变体缺乏剂量补偿相关。相反，在 Sxl 突变体中，我们在雌性 X 染色体上检测到 H4Ac16，这与 X 染色体转录的不适当增加相一致。这些数据表明 H4Ac16 的合成或定位受剂量补偿监管层级控制。剂量补偿可能涉及 H4Ac16 功能，可能通过与 msl 基因产物的相互作用。
Dosage compensation in Drosophila occurs by an increase in transcription of genes on the X chromosome in males. This elevated expression requires the function of at least four loci, known collectively as the male-specific lethal (msl) genes. The proteins encoded by two of these genes, maleless (mle) and male-specific lethal-1 (msl-1), are found associated with the X chromosome in males, suggesting that they act as positive regulators of dosage compensation. A specific acetylated isoform of histone H4, H4Ac16, is also detected predominantly on the male X chromosome. We have found that MLE and MSL-1 bind to the X chromosome in an identical pattern and that the pattern of H4Ac16 on the X is largely coincident with that of MLE/MSL-1. We fail to detect H4Ac16 on the X chromosome in homozygous msl males, correlating with the lack of dosage compensation in these mutants. Conversely, in Sxl mutants, we detect H4Ac16 on the female X chromosomes, coincident with an inappropriate increase in X chromosome transcription. These data suggest that synthesis or localization of H4Ac16 is controlled by the dosage compensation regulatory hierarchy. Dosage compensation may involve H4Ac16 function, potentially through interaction with the products of the msl genes.