期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 75, 期 -, 页码 45-52出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2016.03.013
关键词
NF-E2; TAL1; KLF1; Human adult beta-globin gene; LCR HSs
资金
- National Research Foundation of Korea - Korean Government MEST, Basic Research Promotion Fund [NRF-2012R1A1B5001946, NRF-2013R1A6A3A01027632]
The beta-like globin genes are developmental stage specifically transcribed in erythroid cells. The transcription of the beta-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 beta-globin gene. Here we employed hybrid MEL cells (MEL/ch11) where a human chromosome containing the beta-globin locus is present and the adult beta-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 beta-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 beta-globin gene by allowing the access of activators and cofactors. The roles of activators in the adult beta-globin locus appear to be different from the roles in the early fetal locus. (C) 2016 Elsevier Ltd. All rights reserved.
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