Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors.
Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors.
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DOI：
10.1111/j.1582-4934.2011.01482.x
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发表时间：
2012-08
影响因子：
5.3
通讯作者：
van den Elsen PJ
中科院分区：
文献类型：
--
作者：
Wierda RJ;Kuipers HF;van Eggermond MC;Benard A;van Leeuwen JC;Carluccio S;Geutskens SB;Jukema JW;Marquez VE;Quax PH;van den Elsen PJ
Previously, we have shown that CCR5 transcription is regulated by CREB-1. However, the ubiquitous pattern of CREB-1 expression suggests the involvement of an additional level of transcriptional control in the cell type–specific expression of CCR5. In this study, we show that epigenetic changes (i.e. DNA methylation and histone modifications) within the context of the CCR5 P1 promoter region correlate with transcript levels of CCR5 in healthy and in malignant CD4+ T lymphocytes as well as in CD14+ monocytes. In normal naïve T cells and CD14+ monocytes the CCR5 P1 promoter resembles a bivalent chromatin state, with both repressive and permissive histone methylation and acetylation marks. The CCR5-expressing CD14+ monocytes however show much higher levels of acetylated histone H3 (AcH3) compared to the non–CCR5-expressing naïve T cells. Combined with a highly methylated promoter in CD14+ monocytes, this indicates a dominant role for AcH3 in CCR5 transcription. We also show that pharmacological interference in the epigenetic repressive mechanisms that account for the lack of CCR5 transcription in T leukaemic cell lines results in an increase in CREB-1 association with CCR5 P1 chromatin. Furthermore, RNA polymerase II was also recruited into CCR5 P1 chromatin resulting in CCR5 re-expression. Together, these data indicate that epigenetic modifications of DNA, and of histones, contribute to the control of CCR5 transcription in immune effector cells.
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影响因子：
4.4
作者：
Ke XS;Qu Y;Cheng Y;Li WC;Rotter V;Øyan AM;Kalland KH
通讯作者：
Kalland KH
DOI：
10.1073/pnas.94.5.1925
发表时间：
1997-03-04
影响因子：
11.1
作者：
Bleul, CC;Wu, LJ;Mackay, CR
通讯作者：
Mackay, CR
DOI：
10.1016/j.biopha.2011.03.009
发表时间：
2011-07
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
--
作者：
Banerjee A;Pirrone V;Wigdahl B;Nonnemacher MR
通讯作者：
Nonnemacher MR
影响因子：
4.4
作者：
Holling, Tjadine M.;Bergevoet, Marloes W. T.;Van den Elsen, Peter J.
通讯作者：
Van den Elsen, Peter J.
影响因子：
20.3
作者：
Kuipers, Hedwich F.;Biesta, Paula J.;van den Elsen, Peter J.
通讯作者：
van den Elsen, Peter J.