Histone acetyltransferase p300 regulates the transcription of human erythroid-specific 5-aminolevulinate synthase gene.
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.
Han
Liping
L
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Lu
Jun
J
Pan
Lina
L
Wang
Xiuli
X
Shao
Yangguang
Y
Han
Songyan
S
Huang
Baiqu
B
D000624:5-Aminolevulinate Synthetase / Q000235:genetics* / Q000378:metabolism; D000107:Acetylation; D000756:Anemia, Sideroblastic / Q000201:enzymology / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004920:Erythropoiesis / Q000235:genetics*; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000624:5-Aminolevulinate Synthetase; D018797:Cell Cycle Proteins; D005914:Globins; D051548:Histone Acetyltransferases; D006657:Histones; D012333:RNA, Messenger; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C480079:ALAS2 protein, human