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Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site
Nucleosome depletion at transcription start sites (TSS) has been documented genome-wide in multiple eukaryotic organisms. However, the mechanisms that mediate this nucleosome depletion and its functional impact on transcription remain largely unknown. We have studied these issues at human MHC class...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677874/ https://www.ncbi.nlm.nih.gov/pubmed/19264803 http://dx.doi.org/10.1093/nar/gkp116 |
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author | Leimgruber, Elisa Seguín-Estévez, Queralt Dunand-Sauthier, Isabelle Rybtsova, Natalia Schmid, Christoph D. Ambrosini, Giovanna Bucher, Philipp Reith, Walter |
author_facet | Leimgruber, Elisa Seguín-Estévez, Queralt Dunand-Sauthier, Isabelle Rybtsova, Natalia Schmid, Christoph D. Ambrosini, Giovanna Bucher, Philipp Reith, Walter |
author_sort | Leimgruber, Elisa |
collection | PubMed |
description | Nucleosome depletion at transcription start sites (TSS) has been documented genome-wide in multiple eukaryotic organisms. However, the mechanisms that mediate this nucleosome depletion and its functional impact on transcription remain largely unknown. We have studied these issues at human MHC class II (MHCII) genes. Activation-induced nucleosome free regions (NFR) encompassing the TSS were observed at all MHCII genes. Nucleosome depletion was exceptionally strong, attaining over 250-fold, at the promoter of the prototypical HLA-DRA gene. The NFR was induced primarily by the transcription factor complex that assembles on the conserved promoter-proximal enhancer situated upstream of the TSS. Functional analyses performed in the context of native chromatin demonstrated that displacing the NFR without altering the sequence of the core promoter induced a shift in the position of the TSS. The NFR thus appears to play a critical role in transcription initiation because it directs correct TSS positioning in vivo. Our results provide support for a novel mechanism in transcription initiation whereby the position of the TSS is controlled by nucleosome eviction rather than by promoter sequence. |
format | Text |
id | pubmed-2677874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26778742009-05-15 Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site Leimgruber, Elisa Seguín-Estévez, Queralt Dunand-Sauthier, Isabelle Rybtsova, Natalia Schmid, Christoph D. Ambrosini, Giovanna Bucher, Philipp Reith, Walter Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics Nucleosome depletion at transcription start sites (TSS) has been documented genome-wide in multiple eukaryotic organisms. However, the mechanisms that mediate this nucleosome depletion and its functional impact on transcription remain largely unknown. We have studied these issues at human MHC class II (MHCII) genes. Activation-induced nucleosome free regions (NFR) encompassing the TSS were observed at all MHCII genes. Nucleosome depletion was exceptionally strong, attaining over 250-fold, at the promoter of the prototypical HLA-DRA gene. The NFR was induced primarily by the transcription factor complex that assembles on the conserved promoter-proximal enhancer situated upstream of the TSS. Functional analyses performed in the context of native chromatin demonstrated that displacing the NFR without altering the sequence of the core promoter induced a shift in the position of the TSS. The NFR thus appears to play a critical role in transcription initiation because it directs correct TSS positioning in vivo. Our results provide support for a novel mechanism in transcription initiation whereby the position of the TSS is controlled by nucleosome eviction rather than by promoter sequence. Oxford University Press 2009-05 2009-03-05 /pmc/articles/PMC2677874/ /pubmed/19264803 http://dx.doi.org/10.1093/nar/gkp116 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene Regulation, Chromatin and Epigenetics Leimgruber, Elisa Seguín-Estévez, Queralt Dunand-Sauthier, Isabelle Rybtsova, Natalia Schmid, Christoph D. Ambrosini, Giovanna Bucher, Philipp Reith, Walter Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site |
title | Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site |
title_full | Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site |
title_fullStr | Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site |
title_full_unstemmed | Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site |
title_short | Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site |
title_sort | nucleosome eviction from mhc class ii promoters controls positioning of the transcription start site |
topic | Gene Regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677874/ https://www.ncbi.nlm.nih.gov/pubmed/19264803 http://dx.doi.org/10.1093/nar/gkp116 |
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