Han Liping, Lu Jun, Pan Lina, Wang Xiuli, Shao Yangguang, Han Songyan, Huang Baiqu
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Biochem Biophys Res Commun. 2006 Sep 29;348(3):799-806. doi: 10.1016/j.bbrc.2006.07.147. Epub 2006 Aug 1.
Erythroid-specific 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis of erythroid cells. Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter. Histone acetyltransferase p300 bound withALAS2 promoter and overexpression of p300 increased both the promoter reporter expression and endogenous mRNA level of ALAS2. Additionally, two functional Sp1 sites located in ALAS2 promoter were identified. Both of the GATA-1 sites and all the Sp1 sites at the ALAS2 promoter contributed to the transcription synergistic action with p300. These data implicated a close relationship between the acetylation modification of histone at the ALAS2 promoter and the regulation of this gene. Meanwhile, this work identified that ALAS2 is a novel target gene for p300/CBP action as histone acetyltransferases.
红细胞特异性5-氨基酮戊酸合酶（ALAS2）催化红细胞血红素生物合成中的限速步骤。在此，我们表明用组蛋白去乙酰化酶抑制剂丁酸钠或曲古抑菌素A处理红细胞K562细胞会导致ALAS2基因转录物显著增加，同时ALAS2基因启动子处组蛋白H4的乙酰化水平也增加。组蛋白乙酰转移酶p300与ALAS2启动子结合，p300的过表达增加了启动子报告基因的表达以及ALAS2的内源性mRNA水平。此外，在ALAS2启动子中鉴定出两个功能性Sp1位点。ALAS2启动子处的GATA-1位点和所有Sp1位点都与p300产生转录协同作用。这些数据表明ALAS2启动子处组蛋白的乙酰化修饰与该基因的调控之间存在密切关系。同时，这项工作确定ALAS2是p300/CBP作为组蛋白乙酰转移酶作用的一个新的靶基因。
