title: Changes in DNA methylation of erythroid-specific genes in K562 cells exposed to phenol and hydroquinone.
abstract: Benzene is a common occupational hazard as well as a widespread pollutant. Its metabolites play important roles in its toxicity to the hematopoietic system, but little is known about how benzene metabolites affect erythropoiesis. Our previous study demonstrated that benzene metabolites, including phenol and hydroquinone, inhibited hemin-induced erythroid differentiation of K562 cells. In present study, to elucidate the role of DNA methylation in benzene metabolites-induced inhibition on erythroid differentiation, it was investigated whether DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-CdR), was able to prevent benzene metabolites inhibiting hemin-induced erythroid differentiation in K562 cells, and the methylation levels of erythroid-specific genes in benzene metabolites-treated K562 cells were analyzed by Quantitative MassARRAY methylation analysis platform. It was found that treatment of K562 cells with 5-aza-CdR completely prevented phenol and hydroquinone inhibiting hemin-induced hemoglobin synthesis and hemin-induced expression of erythroid specific genes, including α- and β-globin, erythroid porphobilinogen deaminase and GATA binding protein 1 (GATA-1). Consistently, the exposure to benzene metabolites caused an increase in DNA methylation levels at a few CpG sites in some erythroid specific genes, including α-globin gene and α-cluster HS40 element, β-globin gene and HS core sequence in LCR of β-globin gene cluster, erythroid porphobilinogen deaminase gene, and GATA-1 gene. These results indicated that DNA methylation played a role in benzene metabolites inhibiting hemin-induced erythroid differentiation of K562 cells via down-regulating transcription of some erythroid related genes.
authors: Department of Biological Science and Biotechnology, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
authors: Yang
authors: Y
authors: Li
authors: Xiao-Rong
authors: XR
authors: Wu
authors: Xiao-Fei
authors: XF
authors: Li
authors: Suriguga
authors: Chun-Hong
authors: CH
authors: Yu
authors: Yi-Ran
authors: YR
authors: Li
authors: Zong-Chun
authors: ZC
authors: Yi
mesh_terms: D001374:Azacitidine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018899:CpG Islands; D019175:DNA Methylation; D041905:Erythroid Cells / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects; D050982:GATA1 Transcription Factor / Q000235:genetics; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D011163:Hydroxymethylbilane Synthase / Q000235:genetics; D020014:K562 Cells; D019800:Phenol / Q000633:toxicity*; D055544:beta-Globins / Q000235:genetics; D055545:gamma-Globins / Q000235:genetics
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D006873:Hydroquinones; D055544:beta-Globins; D055545:gamma-Globins; D019800:Phenol; D011163:Hydroxymethylbilane Synthase; D001374:Azacitidine; C031927:hydroquinone
keywords: 5-aza-2′-deoxycytidine; 5-aza-CdR; ALAS2; BFU-E; Benzene metabolites; DNA methylation; DNase I hypersensitive site; Erythroid differentiation; GATA binding protein 1 (globin transcription factor 1); GATA-1; Globin; HS; Hb; Heme; LCR; MALDI-TOF; PARP-1; PBGD; PBS; RT-PCR; SAP; erythroid burst-forming unit; hemoglobin; locus control region; matrix-assisted laser desorption/ionization time-of-flight; phosphate buffered saline; poly(ADP-ribose) polymerases-1; porphobilinogen deaminase; reverse transcriptase-polymerase chain reaction; shrimp alkaline phosphatase; δ-aminolevulinate synthase 2