Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes
The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modific...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/65405 https://orcid.org/0000-0001-9249-8181 |
| _version_ | 1811093034639556608 |
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| author | Lo, Kinyui Alice Bauchmann, Mary K. Baumann, Amy P. Donahue, Christopher J. Thiede, Mark A. Hayes, Lisa S. Des Etages, Shelley Ann G. Fraenkel, Ernest |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Lo, Kinyui Alice Bauchmann, Mary K. Baumann, Amy P. Donahue, Christopher J. Thiede, Mark A. Hayes, Lisa S. Des Etages, Shelley Ann G. Fraenkel, Ernest |
| author_sort | Lo, Kinyui Alice |
| collection | MIT |
| description | The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte transcriptional regulation. |
| first_indexed | 2024-09-23T15:38:28Z |
| format | Article |
| id | mit-1721.1/65405 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:38:28Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/654052022-10-02T03:04:26Z Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes Lo, Kinyui Alice Bauchmann, Mary K. Baumann, Amy P. Donahue, Christopher J. Thiede, Mark A. Hayes, Lisa S. Des Etages, Shelley Ann G. Fraenkel, Ernest Massachusetts Institute of Technology. Department of Biological Engineering Fraenkel, Ernest Lo, Kinyui Alice Fraenkel, Ernest The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte transcriptional regulation. Singapore. Agency for Science, Technology and Research (National Science Scholarship ) Massachusetts Institute of Technology (Eugene Bell Career Development Chair) National Science Foundation (U.S.) (Award No. DBI-0821391) Pfizer Inc. 2011-08-26T15:51:06Z 2011-08-26T15:51:06Z 2011-06 2010-10 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/65405 Lo, Kinyui Alice et al. “Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes.” Ed. Marc Tjwa. PLoS ONE 6.6 (2011) : e19778. https://orcid.org/0000-0001-9249-8181 en_US http://dx.doi.org/10.1371/journal.pone.0019778 PLoS One Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Lo, Kinyui Alice Bauchmann, Mary K. Baumann, Amy P. Donahue, Christopher J. Thiede, Mark A. Hayes, Lisa S. Des Etages, Shelley Ann G. Fraenkel, Ernest Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes |
| title | Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes |
| title_full | Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes |
| title_fullStr | Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes |
| title_full_unstemmed | Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes |
| title_short | Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes |
| title_sort | genome wide profiling of h3k56 acetylation and transcription factor binding sites in human adipocytes |
| url | http://hdl.handle.net/1721.1/65405 https://orcid.org/0000-0001-9249-8181 |
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