Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation
Summary: Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-08-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718311446 |
| _version_ | 1818368637565665280 |
|---|---|
| author | Ryan Raisner Samir Kharbanda Lingyan Jin Edwin Jeng Emily Chan Mark Merchant Peter M. Haverty Russell Bainer Tommy Cheung David Arnott E. Megan Flynn F. Anthony Romero Steven Magnuson Karen E. Gascoigne |
| author_facet | Ryan Raisner Samir Kharbanda Lingyan Jin Edwin Jeng Emily Chan Mark Merchant Peter M. Haverty Russell Bainer Tommy Cheung David Arnott E. Megan Flynn F. Anthony Romero Steven Magnuson Karen E. Gascoigne |
| author_sort | Ryan Raisner |
| collection | DOAJ |
| description | Summary: Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin. Using this approach to dissect the role of H3K27Ac at enhancers, we identify a critical role for this modification in the production of enhancer RNAs and transcription of enhancer-regulated gene networks. : Raisner et al. demonstrate that CBP/P300 bromodomain inhibition reduces levels of the H3K27Ac histone modification specifically at enhancers. Known to be correlated with enhancer activity, the authors find this modification to be essential for enhancer activation, associated gene expression, and proliferation of hematological malignancies. Keywords: enhancer, P300, CBP, bromodomain, histone acetylation, H3K27Ac |
| first_indexed | 2024-12-13T23:11:07Z |
| format | Article |
| id | doaj.art-30f0b373eb01444dbff75e2a8755acdb |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T23:11:07Z |
| publishDate | 2018-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-30f0b373eb01444dbff75e2a8755acdb2022-12-21T23:28:06ZengElsevierCell Reports2211-12472018-08-0124717221729Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 AcetylationRyan Raisner0Samir Kharbanda1Lingyan Jin2Edwin Jeng3Emily Chan4Mark Merchant5Peter M. Haverty6Russell Bainer7Tommy Cheung8David Arnott9E. Megan Flynn10F. Anthony Romero11Steven Magnuson12Karen E. Gascoigne13Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA 94080, USACalico Labs, South San Francisco, CA 94080, USADepartment of Discovery Oncology, Genentech, Inc., South San Francisco, CA 94080, USAProgram in Cancer Biology and Department of Genetics, Stanford University, Stanford, CA 94305, USADepartment of Translational Oncology, Genentech, Inc., South San Francisco, CA 94080, USADepartment of Translational Oncology, Genentech, Inc., South San Francisco, CA 94080, USADepartment of Bioinformatics, Genentech, Inc., South San Francisco, CA 94080, USADepartment of Bioinformatics, Genentech, Inc., South San Francisco, CA 94080, USADepartment of Protein Science, Genentech, Inc., South San Francisco, CA 94080, USADepartment of Protein Science, Genentech, Inc., South San Francisco, CA 94080, USADepartment of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA 94080, USAUnity Biotechnology, Brisbane, CA 94005, USADepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, CA 94080, USADepartment of Discovery Oncology, Genentech, Inc., South San Francisco, CA 94080, USA; Corresponding authorSummary: Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin. Using this approach to dissect the role of H3K27Ac at enhancers, we identify a critical role for this modification in the production of enhancer RNAs and transcription of enhancer-regulated gene networks. : Raisner et al. demonstrate that CBP/P300 bromodomain inhibition reduces levels of the H3K27Ac histone modification specifically at enhancers. Known to be correlated with enhancer activity, the authors find this modification to be essential for enhancer activation, associated gene expression, and proliferation of hematological malignancies. Keywords: enhancer, P300, CBP, bromodomain, histone acetylation, H3K27Achttp://www.sciencedirect.com/science/article/pii/S2211124718311446 |
| spellingShingle | Ryan Raisner Samir Kharbanda Lingyan Jin Edwin Jeng Emily Chan Mark Merchant Peter M. Haverty Russell Bainer Tommy Cheung David Arnott E. Megan Flynn F. Anthony Romero Steven Magnuson Karen E. Gascoigne Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation Cell Reports |
| title | Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation |
| title_full | Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation |
| title_fullStr | Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation |
| title_full_unstemmed | Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation |
| title_short | Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation |
| title_sort | enhancer activity requires cbp p300 bromodomain dependent histone h3k27 acetylation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718311446 |
| work_keys_str_mv | AT ryanraisner enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT samirkharbanda enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT lingyanjin enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT edwinjeng enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT emilychan enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT markmerchant enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT petermhaverty enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT russellbainer enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT tommycheung enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT davidarnott enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT emeganflynn enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT fanthonyromero enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT stevenmagnuson enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation AT karenegascoigne enhanceractivityrequirescbpp300bromodomaindependenthistoneh3k27acetylation |