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Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors
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....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309068/ https://www.ncbi.nlm.nih.gov/pubmed/22050776 http://dx.doi.org/10.1111/j.1582-4934.2011.01482.x |
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author | Wierda, Rutger J Kuipers, Hedwich F van Eggermond, Marja C J A Benard, Anne van Leeuwen, Jan C Carluccio, Silvia Geutskens, Sacha B Jukema, J Wouter Marquez, Victor E Quax, Paul H A van den Elsen, Peter J |
author_facet | Wierda, Rutger J Kuipers, Hedwich F van Eggermond, Marja C J A Benard, Anne van Leeuwen, Jan C Carluccio, Silvia Geutskens, Sacha B Jukema, J Wouter Marquez, Victor E Quax, Paul H A van den Elsen, Peter J |
author_sort | Wierda, Rutger J |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3309068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-33090682013-08-01 Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors Wierda, Rutger J Kuipers, Hedwich F van Eggermond, Marja C J A Benard, Anne van Leeuwen, Jan C Carluccio, Silvia Geutskens, Sacha B Jukema, J Wouter Marquez, Victor E Quax, Paul H A van den Elsen, Peter J J Cell Mol Med Original Articles 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. Blackwell Publishing Ltd 2012-08 2012-07-29 /pmc/articles/PMC3309068/ /pubmed/22050776 http://dx.doi.org/10.1111/j.1582-4934.2011.01482.x Text en Copyright © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
spellingShingle | Original Articles Wierda, Rutger J Kuipers, Hedwich F van Eggermond, Marja C J A Benard, Anne van Leeuwen, Jan C Carluccio, Silvia Geutskens, Sacha B Jukema, J Wouter Marquez, Victor E Quax, Paul H A van den Elsen, Peter J Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors |
title | Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors |
title_full | Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors |
title_fullStr | Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors |
title_full_unstemmed | Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors |
title_short | Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors |
title_sort | epigenetic control of ccr5 transcript levels in immune cells and modulation by small molecules inhibitors |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309068/ https://www.ncbi.nlm.nih.gov/pubmed/22050776 http://dx.doi.org/10.1111/j.1582-4934.2011.01482.x |
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