Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci

Anna Stornaiuolo, Dario Acampora, Maria Pannese, Maurizio D'Esposito, Franco Morelli, Enrica Migliaccio, Marco Rambaldi, Antonio Faiella, Vincenzo Nigro, Antonio Simeone, Edoardo Boncinelli
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引用次数: 55

Abstract

We studied the expression of 33 human homeobox genes belonging to four complex HOX loci in embryonal carcinoma NT2/D1 cells. These cells can be induced to differentiate by culturing them in media containing retinoic acid. Northern blot analysis reveals that no expression of these genes was detectable in NT2/D1 stem cells, whereas 22 HOX genes are well expressed in NT2/D1 cells treated with 10 μM retinoic acid for 14 days. The 11 HOX genes the expression of which remained undetectable in NT2/D1 cells after this treatment are located at the 5′ end of their loci: four in HOX1, five in HOX3 and two in HOX4. The boundary between induced and silent genes roughly corresponds to the HOX genes constituting the homology group 5, related to the Abdominal-B homeotic gene of Drosophila. All nine identified HOX2 genes are well expressed in fully induced NT2/D1 cells and none of them maps 5′ genes of this homology group. We conclude that HOX genes are differentially activated by retinoic acid in these cells according to their physical location within the four chromosomal loci.

人类HOX基因在胚胎癌细胞中被视黄酸不同地激活,取决于它们在四个基因座中的位置
我们研究了属于4个复杂HOX位点的33个人同源盒基因在胚胎癌NT2/D1细胞中的表达。这些细胞可以通过在含有维甲酸的培养基中培养而诱导分化。Northern blot分析显示,这些基因在NT2/D1干细胞中未检测到表达,而22个HOX基因在10 μM维甲酸处理14天的NT2/D1干细胞中表达良好。处理后在NT2/D1细胞中未检测到表达的11个HOX基因位于其基因座的5 '端:HOX1中有4个,HOX3中有5个,HOX4中有2个。诱导基因和沉默基因的边界大致对应于构成同源群5的HOX基因,与果蝇的腹部- b同源基因有关。所有鉴定的9个HOX2基因在完全诱导的NT2/D1细胞中均表达良好,且没有一个基因映射该同源群的5′基因。我们得出结论,这些细胞中的HOX基因根据其在四个染色体位点中的物理位置而被视黄酸不同地激活。
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