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CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands

BACKGROUND: The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood. This is particularly important at regulatory regions, such as CpG islands (CGIs), which are known to recruit Trithorax (TrxG) and Polyco...

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Autores principales: van de Lagemaat, Louie N., Flenley, Maria, Lynch, Magnus D., Garrick, David, Tomlinson, Simon R., Kranc, Kamil R., Vernimmen, Douglas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173865/
https://www.ncbi.nlm.nih.gov/pubmed/30292235
http://dx.doi.org/10.1186/s13072-018-0230-0
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author van de Lagemaat, Louie N.
Flenley, Maria
Lynch, Magnus D.
Garrick, David
Tomlinson, Simon R.
Kranc, Kamil R.
Vernimmen, Douglas
author_facet van de Lagemaat, Louie N.
Flenley, Maria
Lynch, Magnus D.
Garrick, David
Tomlinson, Simon R.
Kranc, Kamil R.
Vernimmen, Douglas
author_sort van de Lagemaat, Louie N.
collection PubMed
description BACKGROUND: The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood. This is particularly important at regulatory regions, such as CpG islands (CGIs), which are known to recruit Trithorax (TrxG) and Polycomb group proteins. The CxxC zinc finger protein 1 (CFP1, also known as CGBP) is a subunit of the TrxG SET1 protein complex, a major catalyst of trimethylation of H3K4 (H3K4me3). RESULTS: Here, we used ChIP followed by high-throughput sequencing (ChIP-seq) to analyse genomic occupancy of CFP1 in two human haematopoietic cell types. We demonstrate that CFP1 occupies CGIs associated with active transcription start sites (TSSs), and is mutually exclusive with H3K27 trimethylation (H3K27me3), a marker of polycomb repressive complex 2. Strikingly, rather than being restricted to active CGI TSSs, CFP1 also occupies a substantial fraction of active non-CGI TSSs and enhancers of transcribed genes. However, relative to other TrxG subunits, CFP1 was specialised to TSSs. Finally, we found enrichment of CpG-containing DNA motifs in CFP1 peaks at CGI promoters. CONCLUSIONS: We found that CFP1 is not solely recruited to CpG islands as it was originally defined, but also other regions including non-CpG island promoters and enhancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13072-018-0230-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-61738652018-10-15 CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands van de Lagemaat, Louie N. Flenley, Maria Lynch, Magnus D. Garrick, David Tomlinson, Simon R. Kranc, Kamil R. Vernimmen, Douglas Epigenetics Chromatin Research BACKGROUND: The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood. This is particularly important at regulatory regions, such as CpG islands (CGIs), which are known to recruit Trithorax (TrxG) and Polycomb group proteins. The CxxC zinc finger protein 1 (CFP1, also known as CGBP) is a subunit of the TrxG SET1 protein complex, a major catalyst of trimethylation of H3K4 (H3K4me3). RESULTS: Here, we used ChIP followed by high-throughput sequencing (ChIP-seq) to analyse genomic occupancy of CFP1 in two human haematopoietic cell types. We demonstrate that CFP1 occupies CGIs associated with active transcription start sites (TSSs), and is mutually exclusive with H3K27 trimethylation (H3K27me3), a marker of polycomb repressive complex 2. Strikingly, rather than being restricted to active CGI TSSs, CFP1 also occupies a substantial fraction of active non-CGI TSSs and enhancers of transcribed genes. However, relative to other TrxG subunits, CFP1 was specialised to TSSs. Finally, we found enrichment of CpG-containing DNA motifs in CFP1 peaks at CGI promoters. CONCLUSIONS: We found that CFP1 is not solely recruited to CpG islands as it was originally defined, but also other regions including non-CpG island promoters and enhancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13072-018-0230-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-06 /pmc/articles/PMC6173865/ /pubmed/30292235 http://dx.doi.org/10.1186/s13072-018-0230-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
van de Lagemaat, Louie N.
Flenley, Maria
Lynch, Magnus D.
Garrick, David
Tomlinson, Simon R.
Kranc, Kamil R.
Vernimmen, Douglas
CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands
title CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands
title_full CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands
title_fullStr CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands
title_full_unstemmed CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands
title_short CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands
title_sort cpg binding protein (cfp1) occupies open chromatin regions of active genes, including enhancers and non-cpg islands
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173865/
https://www.ncbi.nlm.nih.gov/pubmed/30292235
http://dx.doi.org/10.1186/s13072-018-0230-0
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