author_facet Brinkman, Arie B.
Gu, Hongcang
Bartels, Stefanie J.J.
Zhang, Yingying
Matarese, Filomena
Simmer, Femke
Marks, Hendrik
Bock, Christoph
Gnirke, Andreas
Meissner, Alexander
Stunnenberg, Hendrik G.
Brinkman, Arie B.
Gu, Hongcang
Bartels, Stefanie J.J.
Zhang, Yingying
Matarese, Filomena
Simmer, Femke
Marks, Hendrik
Bock, Christoph
Gnirke, Andreas
Meissner, Alexander
Stunnenberg, Hendrik G.
author Brinkman, Arie B.
Gu, Hongcang
Bartels, Stefanie J.J.
Zhang, Yingying
Matarese, Filomena
Simmer, Femke
Marks, Hendrik
Bock, Christoph
Gnirke, Andreas
Meissner, Alexander
Stunnenberg, Hendrik G.
spellingShingle Brinkman, Arie B.
Gu, Hongcang
Bartels, Stefanie J.J.
Zhang, Yingying
Matarese, Filomena
Simmer, Femke
Marks, Hendrik
Bock, Christoph
Gnirke, Andreas
Meissner, Alexander
Stunnenberg, Hendrik G.
Genome Research
Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
Genetics (clinical)
Genetics
author_sort brinkman, arie b.
spelling Brinkman, Arie B. Gu, Hongcang Bartels, Stefanie J.J. Zhang, Yingying Matarese, Filomena Simmer, Femke Marks, Hendrik Bock, Christoph Gnirke, Andreas Meissner, Alexander Stunnenberg, Hendrik G. 1088-9051 Cold Spring Harbor Laboratory Genetics (clinical) Genetics http://dx.doi.org/10.1101/gr.133728.111 <jats:p>Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here, we present sequential ChIP-bisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA methylation patterns associated with chromatin modifications or chromatin-associated factors directly. A chromatin-immunoprecipitation (ChIP)-capturing step is used to obtain a restricted representation of the genome occupied by the epigenetic feature of interest, for which a single-base resolution DNA methylation map is then generated. When applied to H3 lysine 27 trimethylation (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout most of the genome, except for CpG islands, where these two marks are mutually exclusive. Further ChIP-BS-seq-based analysis in <jats:italic>Dnmt</jats:italic> triple-knockout (TKO) embryonic stem cells revealed that total loss of CpG methylation is associated with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed. At an even broader scale, these BLOCs correspond to regions of high DNA methylation in wild-type ES cells, suggesting that DNA methylation prevents H3K27me3 deposition locally and at a megabase scale. Our strategy provides a unique way of investigating global interdependencies between DNA methylation and other chromatin features.</jats:p> Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk Genome Research
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title Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_unstemmed Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_full Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_fullStr Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_full_unstemmed Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_short Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_sort sequential chip-bisulfite sequencing enables direct genome-scale investigation of chromatin and dna methylation cross-talk
topic Genetics (clinical)
Genetics
url http://dx.doi.org/10.1101/gr.133728.111
publishDate 2012
physical 1128-1138
description <jats:p>Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here, we present sequential ChIP-bisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA methylation patterns associated with chromatin modifications or chromatin-associated factors directly. A chromatin-immunoprecipitation (ChIP)-capturing step is used to obtain a restricted representation of the genome occupied by the epigenetic feature of interest, for which a single-base resolution DNA methylation map is then generated. When applied to H3 lysine 27 trimethylation (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout most of the genome, except for CpG islands, where these two marks are mutually exclusive. Further ChIP-BS-seq-based analysis in <jats:italic>Dnmt</jats:italic> triple-knockout (TKO) embryonic stem cells revealed that total loss of CpG methylation is associated with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed. At an even broader scale, these BLOCs correspond to regions of high DNA methylation in wild-type ES cells, suggesting that DNA methylation prevents H3K27me3 deposition locally and at a megabase scale. Our strategy provides a unique way of investigating global interdependencies between DNA methylation and other chromatin features.</jats:p>
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author Brinkman, Arie B., Gu, Hongcang, Bartels, Stefanie J.J., Zhang, Yingying, Matarese, Filomena, Simmer, Femke, Marks, Hendrik, Bock, Christoph, Gnirke, Andreas, Meissner, Alexander, Stunnenberg, Hendrik G.
author_facet Brinkman, Arie B., Gu, Hongcang, Bartels, Stefanie J.J., Zhang, Yingying, Matarese, Filomena, Simmer, Femke, Marks, Hendrik, Bock, Christoph, Gnirke, Andreas, Meissner, Alexander, Stunnenberg, Hendrik G., Brinkman, Arie B., Gu, Hongcang, Bartels, Stefanie J.J., Zhang, Yingying, Matarese, Filomena, Simmer, Femke, Marks, Hendrik, Bock, Christoph, Gnirke, Andreas, Meissner, Alexander, Stunnenberg, Hendrik G.
author_sort brinkman, arie b.
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description <jats:p>Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here, we present sequential ChIP-bisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA methylation patterns associated with chromatin modifications or chromatin-associated factors directly. A chromatin-immunoprecipitation (ChIP)-capturing step is used to obtain a restricted representation of the genome occupied by the epigenetic feature of interest, for which a single-base resolution DNA methylation map is then generated. When applied to H3 lysine 27 trimethylation (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout most of the genome, except for CpG islands, where these two marks are mutually exclusive. Further ChIP-BS-seq-based analysis in <jats:italic>Dnmt</jats:italic> triple-knockout (TKO) embryonic stem cells revealed that total loss of CpG methylation is associated with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed. At an even broader scale, these BLOCs correspond to regions of high DNA methylation in wild-type ES cells, suggesting that DNA methylation prevents H3K27me3 deposition locally and at a megabase scale. Our strategy provides a unique way of investigating global interdependencies between DNA methylation and other chromatin features.</jats:p>
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spelling Brinkman, Arie B. Gu, Hongcang Bartels, Stefanie J.J. Zhang, Yingying Matarese, Filomena Simmer, Femke Marks, Hendrik Bock, Christoph Gnirke, Andreas Meissner, Alexander Stunnenberg, Hendrik G. 1088-9051 Cold Spring Harbor Laboratory Genetics (clinical) Genetics http://dx.doi.org/10.1101/gr.133728.111 <jats:p>Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here, we present sequential ChIP-bisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA methylation patterns associated with chromatin modifications or chromatin-associated factors directly. A chromatin-immunoprecipitation (ChIP)-capturing step is used to obtain a restricted representation of the genome occupied by the epigenetic feature of interest, for which a single-base resolution DNA methylation map is then generated. When applied to H3 lysine 27 trimethylation (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout most of the genome, except for CpG islands, where these two marks are mutually exclusive. Further ChIP-BS-seq-based analysis in <jats:italic>Dnmt</jats:italic> triple-knockout (TKO) embryonic stem cells revealed that total loss of CpG methylation is associated with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed. At an even broader scale, these BLOCs correspond to regions of high DNA methylation in wild-type ES cells, suggesting that DNA methylation prevents H3K27me3 deposition locally and at a megabase scale. Our strategy provides a unique way of investigating global interdependencies between DNA methylation and other chromatin features.</jats:p> Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk Genome Research
spellingShingle Brinkman, Arie B., Gu, Hongcang, Bartels, Stefanie J.J., Zhang, Yingying, Matarese, Filomena, Simmer, Femke, Marks, Hendrik, Bock, Christoph, Gnirke, Andreas, Meissner, Alexander, Stunnenberg, Hendrik G., Genome Research, Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk, Genetics (clinical), Genetics
title Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_full Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_fullStr Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_full_unstemmed Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_short Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
title_sort sequential chip-bisulfite sequencing enables direct genome-scale investigation of chromatin and dna methylation cross-talk
title_unstemmed Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk
topic Genetics (clinical), Genetics
url http://dx.doi.org/10.1101/gr.133728.111