Noncanonical compensation of zygotic X transcription in early Drosophila melanogaster development revealed through single-embryo RNA-seq.
Noncanonical compensation of zygotic X transcription in early Drosophila melanogaster development revealed through single-embryo RNA-seq.
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DOI：
10.1371/journal.pbio.1000590
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发表时间：
2011-02-08
期刊：
影响因子：
9.8
通讯作者：
Eisen MB
中科院分区：
文献类型：
--
作者：
Lott SE;Villalta JE;Schroth GP;Luo S;Tonkin LA;Eisen MB
在建立MSL介导的剂量补偿之前，来自X染色体的许多基因在果蝇发育早期的雌性和雄性胚胎中以相同的水平表达，这表明存在一种新的机制。当黑腹果蝇胚胎在有丝分裂周期10左右启动合子转录时，X染色体上的特定基因的剂量敏感性表达触发了性别决定级联反应，该级联反应通过超转录雄性中的单个X染色体来补偿性染色体剂量的差异。然而，在合子转录的开始和接近有丝分裂周期14结束的典型剂量补偿的建立之间有大约1小时的延迟。在此期间，合子转录驱动分割，细胞化和其他重要的发育事件。由于参与这些过程的许多基因位于X染色体上，我们想知道它们是否在女性中以更高的水平转录，以及这是否可能导致性别特异性的早期胚胎模式。为了研究这种可能性，我们开发了精确分期、性别和表征单个胚胎转录组的方法。我们在8个时间点测量了男性和女性胚胎的全基因组mRNA丰度，跨越有丝分裂周期10到晚期周期14，使用亲本系之间的多态性来区分母体和合子转录。我们发现有限的性别特异性合子转录，在X上的基因在女性中以较高水平表达的趋势较弱。然而，男性中来自单个X染色体的转录物比女性中来自任一X染色体的转录物更丰富，表明在典型的MSL介导的剂量补偿系统激活之前存在广泛的剂量补偿。重要的是，这种早期合子剂量补偿的新系统导致在男性和女性胚胎中，关键的X连锁发育调节因子，包括巨大（gt），布林克（brk），buttonhead（btd）和短原肠胚形成（sog）的转录水平几乎相同。基因剂量的变化会对动物的发育产生深远的影响。然而，每一代动物都必须科普性染色体数量的差异。果蝇通过一种机制来补偿X染色体剂量的差异（雌性两条，雄性一条），这种机制允许雄性更多地转录单个X染色体。但这种机制直到胚胎开始转录后一个多小时才建立，在此期间发生了许多重要的发育事件，如细胞化和分割。在这里，我们使用的mRNA测序方法来表征基因表达在个别女性和男性胚胎发病之前，以前的特征剂量补偿系统。虽然我们在女性中发现更多来自X染色体基因的转录本，但我们也发现许多基因在男性和女性中具有相同的转录水平。这些结果表明，有一种替代机制，以补偿剂量作用在早期的发展，在发病之前，以前的特点剂量补偿系统。
Mmany genes from the X chromosome are expressed at the same level in female and male embryos during early Drosophila development, prior to the establishment of MSL-mediated dosage compensation, suggesting the existence of a novel mechanism. When Drosophila melanogaster embryos initiate zygotic transcription around mitotic cycle 10, the dose-sensitive expression of specialized genes on the X chromosome triggers a sex-determination cascade that, among other things, compensates for differences in sex chromosome dose by hypertranscribing the single X chromosome in males. However, there is an approximately 1 hour delay between the onset of zygotic transcription and the establishment of canonical dosage compensation near the end of mitotic cycle 14. During this time, zygotic transcription drives segmentation, cellularization, and other important developmental events. Since many of the genes involved in these processes are on the X chromosome, we wondered whether they are transcribed at higher levels in females and whether this might lead to sex-specific early embryonic patterning. To investigate this possibility, we developed methods to precisely stage, sex, and characterize the transcriptomes of individual embryos. We measured genome-wide mRNA abundance in male and female embryos at eight timepoints, spanning mitotic cycle 10 through late cycle 14, using polymorphisms between parental lines to distinguish maternal and zygotic transcription. We found limited sex-specific zygotic transcription, with a weak tendency for genes on the X to be expressed at higher levels in females. However, transcripts derived from the single X chromosome in males were more abundant that those derived from either X chromosome in females, demonstrating that there is widespread dosage compensation prior to the activation of the canonical MSL-mediated dosage compensation system. Crucially, this new system of early zygotic dosage compensation results in nearly identical transcript levels for key X-linked developmental regulators, including giant (gt), brinker (brk), buttonhead (btd), and short gastrulation (sog), in male and female embryos. Variation in gene dose can have profound effects on animal development. Yet every generation, animals must cope with differences in sex chromosome numbers. Drosophila compensate for the difference in X chromosome dosage (two in females, one in males) with a mechanism that allows for more transcription of the single X chromosome in males. But this mechanism is not established until over an hour after the embryo begins transcription, during which time a number of important events in development occur such as cellularization and segmentation. Here we use an mRNA sequencing method to characterize gene expression in individual female and male embryos before the onset of the previously characterized dosage compensation system. While we find more transcripts from X chromosomal genes in females, we also find many genes with equal transcript levels in males and females. These results indicate that there is an alternate mechanism to compensate for dosage acting earlier in development, prior to the onset of the previously characterized dosage compensation system.
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DOI：
10.1083/jcb.141.1.5
发表时间：
1998-04-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fung JC;Marshall WF;Dernburg A;Agard DA;Sedat JW
通讯作者：
Sedat JW
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
EDGAR, BA;SCHUBIGER, G
通讯作者：
SCHUBIGER, G
影响因子：
10.5
作者：
JIANG, J;HOEY, T;LEVINE, M
通讯作者：
LEVINE, M
DOI：
10.1007/bf01959597
发表时间：
1928-01-01
期刊：
Zeitschrift fuer Induktive Abstammungs- und Vererbungslehre
影响因子：
--
作者：
Bridges, C. B.;Mabritschevsky, E.
通讯作者：
Mabritschevsky, E.