Transcriptional activation of the gamma-globin gene in baboons treated with decitabine and in cultured erythroid progenitor cells involves different mechanisms.
Transcriptional activation of the gamma-globin gene in baboons treated with decitabine and in cultured erythroid progenitor cells involves different mechanisms.
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DOI：
10.1016/j.exphem.2009.06.007
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发表时间：
2009-10
影响因子：
2.6
通讯作者：
Lavelle D
中科院分区：
文献类型：
--
作者：
Chin J;Singh M;Banzon V;Vaitkus K;Ibanez V;Kouznetsova T;Mahmud N;DeSimone J;Lavelle D
To investigate the mechanism(s) responsible for increased γ-globin expression in vivo in decitabine-treated baboons and in vitro in cultured erythroid progenitor cells (EPC) from adult baboon bone marrow (BM). Fetal liver, adult BM erythroid cells pre- and post-decitabine, and cultured EPCs were analyzed for distribution of RNA polymerase II, histone acetylation, and histone H3 (lys4) trimethyl throughout the γ-globin gene complex by chromatin immunoprecipitation. DNA methylation of the γ-globin promoter was determined by bisulfite sequencing. Expression of the baboon Iγ- and Vγ-globin chains was determined by high performance liquid chromatography (HPLC). Expression of BCL11A, a recently identified repressor of γ-globin expression, was analyzed by Western blot. Increased γ-globin expression in decitabine-treated baboons and cultured EPC correlated with increased levels of RNA polymerase II, histone acetylation, and histone H3 (lys4) trimethyl associated with the γ-globin gene consistent with a transcriptional activation mechanism. Cultured EPC expressed the Iγ- and Vγ-globin chains in a pattern characteristic of fetal development. The level of DNA methylation of the γ-globin gene promoter in EPC cultures was similar to BM erythroid cells from normal adult baboons. Different BCL11A isoforms were observed in BM erythroid cells and cultured EPC. The mechanism responsible for increased γ-globin expression in cultured EPC was unexpectedly not associated with increased DNA hypomethylation of the γ-globin gene promoter compared to normal BM erythroid cells, in contrast to BM erythroid cells of decitabine-treated baboons. Rather, increased fetal hemoglobin in EPC cultures was associated with a fetal Iγ/Vγ chain ratio and a difference in the size of the BCL11A protein compared to normal BM erythroid cells.
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影响因子：
20.3
作者：
Chen, YH;Lavelle, D;Hankewych, M
通讯作者：
Hankewych, M
影响因子：
20.3
作者：
Fathallah, Hassana;Weinberg, Rona S.;Atweh, George F.
通讯作者：
Atweh, George F.
影响因子：
3.7
作者：
Goren, Alon;Simchen, Giora;Fibach, Eitan;Szabo, Piroska E.;Tanimoto, Keiji;Chakalova, Lyubomira;Pfeifer, Gerd P.;Fraser, Peter J.;Engel, James D.;Cedar, Howard
通讯作者：
Cedar, Howard
DOI：
10.1073/pnas.79.14.4428
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DESIMONE, J;HELLER, P;ZWIERS, D
通讯作者：
ZWIERS, D
影响因子：
2.3
作者：
Lavelle, D;Vaitkus, K;DeSimone, J
通讯作者：
DeSimone, J