title: Erythroid activator NF-E2, TAL1 and KLF1 play roles in forming the LCR HSs in the human adult β-globin locus.
abstract: The β-like globin genes are developmental stage specifically transcribed in erythroid cells. The transcription of the β-like globin genes requires erythroid specific activators such as GATA-1, NF-E2, TAL1 and KLF1. However, the roles of these activators have not fully elucidated in transcription of the human adult β-globin gene. Here we employed hybrid MEL cells (MEL/ch11) where a human chromosome containing the β-globin locus is present and the adult β-globin gene is highly transcribed by induction. The roles of erythroid specific activators were analyzed by inhibiting the expression of NF-E2, TAL1 or KLF1 in MEL/ch11 cells. The loss of each activator decreased the transcription of human β-globin gene, locus wide histone hyperacetylation and the binding of other erythroid specific activators including GATA-1, even though not affecting the expression of other activators. Notably, sensitivity to DNase I was reduced in the locus control region (LCR) hypersensitive sites (HSs) with the depletion of activators. These results indicate that NF-E2, TAL1 and KLF1, all activators play a primary role in HSs formation in the LCR. It might contribute to the transcription of human adult β-globin gene by allowing the access of activators and cofactors. The roles of activators in the adult β-globin locus appear to be different from the roles in the early fetal locus.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Yea Woon
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Won Ju
authors.initials: WJ
authors.lastname: Yun
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea. Electronic address: kimaeri@pusan.ac.kr.
authors.forename: AeRi
authors.initials: A
authors.lastname: Kim
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D041905:Erythroid Cells / Q000378:metabolism*; D056426:Genetic Loci / Q000235:genetics*; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D019901:Locus Control Region / Q000235:genetics*; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014158:Transcription, Genetic / Q000235:genetics; D055544:beta-Globins / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006657:Histones; D051741:Kruppel-Like Transcription Factors; D050984:NF-E2 Transcription Factor, p45 Subunit; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D055544:beta-Globins; C494692:NFE2 protein, human; C080774:erythroid Kruppel-like factor; C067143:TAL1 protein, human
keywords: Human adult β-globin gene; KLF1; LCR HSs; NF-E2; TAL1