A set of proteins and noncoding RNAs, referred to as the male specific lethal （MSL） complex, is present on the male X chromosome in Drosophila and has been postulated to be responsible for dosage compensation of thi...A set of proteins and noncoding RNAs, referred to as the male specific lethal （MSL） complex, is present on the male X chromosome in Drosophila and has been postulated to be responsible for dosage compensation of this chromosome -- the up-regulation of its expression to be equal to that of two X chromosomes in females. This hypothesis is evaluated in view of lesser known aspects of dosage compensation such as the fact that metafemales with three X chromosomes also have equal expression to normal females, which would require a down-regulation of each gene copy Moreover, when this complex is ectopically expressed in females or specifically targeted to a reporter in males, there is no increase in expression of the genes or targets with which it is associated. These observations are not consistent with the hypothesis that the MSL complex conditions dosage compensation. A synthesis is described that can account for these observations.展开更多
Dosage compensation refers to the equal expression between the sexes despite the fact that the dosage of the X chromosome is different in males and females.In Drosophila there is a twofold upregulation of the single m...Dosage compensation refers to the equal expression between the sexes despite the fact that the dosage of the X chromosome is different in males and females.In Drosophila there is a twofold upregulation of the single male X.In triple X metafemales,there is also dosage compensation,which occurs by a two-thirds downregulation.There is a concomitant reduction in expression of many autosomal genes in metafemales.The male specific lethal(MSL)complex is present on the male X chromosome.Evidence is discussed showing that the MSL complex sequesters a histone acetyltransferase to the X chromosome to mute an otherwise increased expression by diminishing the histone acetylation on the autosomes.Several lines of evidence indicate that a constraining activity occurs from the MSL complex to prevent overcompensation on the X that might otherwise occur from the high level of acetylation present.Together,the evidence suggests that dosage compensation is a modification of a regulatory inverse dosage effect that is a reflection of intrinsic gene regulatory mechanisms and that the MSL complex has evolved in reaction in order to equalize the expression on both the X and autosomes of males and females.展开更多
基金supported by the National Institutes of Health grant of the United States(No.RO1GM068042)
文摘A set of proteins and noncoding RNAs, referred to as the male specific lethal （MSL） complex, is present on the male X chromosome in Drosophila and has been postulated to be responsible for dosage compensation of this chromosome -- the up-regulation of its expression to be equal to that of two X chromosomes in females. This hypothesis is evaluated in view of lesser known aspects of dosage compensation such as the fact that metafemales with three X chromosomes also have equal expression to normal females, which would require a down-regulation of each gene copy Moreover, when this complex is ectopically expressed in females or specifically targeted to a reporter in males, there is no increase in expression of the genes or targets with which it is associated. These observations are not consistent with the hypothesis that the MSL complex conditions dosage compensation. A synthesis is described that can account for these observations.
基金supported by National Institutes of Health grant RO1GM068042-05.
文摘Dosage compensation refers to the equal expression between the sexes despite the fact that the dosage of the X chromosome is different in males and females.In Drosophila there is a twofold upregulation of the single male X.In triple X metafemales,there is also dosage compensation,which occurs by a two-thirds downregulation.There is a concomitant reduction in expression of many autosomal genes in metafemales.The male specific lethal(MSL)complex is present on the male X chromosome.Evidence is discussed showing that the MSL complex sequesters a histone acetyltransferase to the X chromosome to mute an otherwise increased expression by diminishing the histone acetylation on the autosomes.Several lines of evidence indicate that a constraining activity occurs from the MSL complex to prevent overcompensation on the X that might otherwise occur from the high level of acetylation present.Together,the evidence suggests that dosage compensation is a modification of a regulatory inverse dosage effect that is a reflection of intrinsic gene regulatory mechanisms and that the MSL complex has evolved in reaction in order to equalize the expression on both the X and autosomes of males and females.
