Chromosomal binding sites of the homeotic cofactor Homothorax
Chromosomal binding sites of the homeotic cofactor Homothorax
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DOI：
10.1007/s00438-008-0347-0
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发表时间：
2008-07-01
影响因子：
3.1
通讯作者：
Salzberg, Adi
中科院分区：
文献类型：
--
作者：
Cohen, Lior;Salzberg, Adi
Meis 家族癌蛋白在白血病发生中发挥着至关重要的作用，并且在其他类型的癌症中也高度表达。 Meis蛋白的转化潜力取决于它们激活基因表达的能力，因此揭示其靶基因的身份非常重要。果蝇的基因组包含一个 Meis 基因，即同胸 (hth)，该基因在胚胎和成虫发育中发挥多种作用。 hth 突变影响许多胚胎和成体组织的发育，表明 Hth 调节大量基因的转录。然而，目前尚不清楚有多少基因直接受Hth调控以及这些基因的性质是什么。为了解决这个问题，我们检查了 Hth 在多线染色体上的体内结合位点的分布。我们发现，在第三龄幼虫的唾液腺 (SG) 中，Hth 以非常可重复的模式与大约 150 个染色体位点结合。其中数百个位点已被细胞学绘制。有趣的是，Hth 在一些最重要的激素诱导的染色体泡中积累高水平，这表明 Hth 在蜕皮激素诱导的靶点激活中可能发挥作用。干扰幼虫 SG 中 Hth 的正常转录活性会导致细胞大小和 DNA 含量急剧减少，这表明 Hth 参与幼虫 SG 中细胞生长和内复制的调节。
The Meis family oncoproteins play a crucial role in leukemogenesis and are highly expressed in other types of cancer as well. The transforming potential of Meis proteins depends on their ability to activate gene expression and therefore, revealing the identity of their target genes is very important. The genome of the fruit fly Drosophila melanogaster contains a single Meis gene, homothorax (hth), which plays multiple roles in embryonic and adult development. Mutations in hth affect the development of numerous embryonic and adult tissues, suggesting that Hth regulates the transcription of a large number of genes. However, it is not known how many genes are regulated directly by Hth and what is the nature of these genes. To address this question, we examined the distribution of the in vivo binding sites of Hth on polytene chromosomes. We found that in the salivary glands (SG) of third instar larvae, Hth binds to approximately 150 chromosomal sites in a very reproducible pattern. More than hundred of these sites were mapped cytologically. Interestingly, Hth accumulates at high levels in some of the most prominent hormone-induced chromosomal puffs, pointing to a possible role of Hth in activation of ecdysone-induced targets. Interfering with the normal transcriptional activity of Hth in larval SGs leads to dramatic reduction in cell size and DNA content implicating Hth in the regulation of cell growth and endoreplication in larval SGs.