Sodium butyrate activates erythroid-specific 5-aminolevulinate synthase gene through Sp1 elements at its promoter.
Sodium butyrate (NaBu) has been shown to induce erythroid cell differentiation. In this study, we investigated the mechanisms involved in NaBu-induced activation of erythroid-specific 5-aminolevulinate synthase gene (ALAS2). We showed that NaBu upregulated ALAS2 gene transcription in different cell lineages. By using site-directed mutagenesis of putative responsive elements at ALAS2 promoter and reporter gene analysis, we identified that the Sp1 binding sites within the ALAS2 promoter were responsive to NaBu stimulation. Results from the chromatin immunoprecipitation (ChIP) assays indicated that upon the NaBu stimulation, binding of Sp1 protein to ALAS2 promoter increased significantly, with concurrent increases in acetylation level of histone H3 and dimethylation level of H3-Lysine4 at ALAS2 promoter. Also, our data suggested that HDAC1 may be a target enzyme of NaBu action.
Han
Liping
L
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, PR China.
Zhong
Yun
Y
Huang
Binlu
B
Han
Limei
L
Pan
Lina
L
Xu
Xin
X
Wang
Xiuli
X
Huang
Baiqu
B
Lu
Jun
J
D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D000107:Acetylation; D002087:Butyrates / Q000494:pharmacology; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D041905:Erythroid Cells / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D002087:Butyrates; D006657:Histones; D016329:Sp1 Transcription Factor; D000624:5-Aminolevulinate Synthetase; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases