H3K4me3 breadth is linked to cell identity and transcriptional consistency
Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and fu...
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| Published in: | Cell Vol. 158; no. 3; p. 673 |
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| Main Authors: | , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
31.07.2014
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| Subjects: | |
| ISSN: | 1097-4172, 1097-4172 |
| Online Access: | Get more information |
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| Abstract | Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. The broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by the broadest H3K4me3 domains exhibit enhanced transcriptional consistency and [corrected] increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes. |
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| AbstractList | Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. The broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by the broadest H3K4me3 domains exhibit enhanced transcriptional consistency and [corrected] increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes.Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. The broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by the broadest H3K4me3 domains exhibit enhanced transcriptional consistency and [corrected] increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes. Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. The broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by the broadest H3K4me3 domains exhibit enhanced transcriptional consistency and [corrected] increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes. |
| Author | Devarajan, Keerthana Benayoun, Bérénice A Gupta, Rakhi Wong, Edith D Snyder, Michael P Brunet, Anne Mahmoudi, Salah Ucar, Duygu Baker, Julie C Mancini, Elena Cherry, J Michael Karra, Kalpana Pollina, Elizabeth A Kundaje, Anshul B Daugherty, Aaron C Hitz, Benjamin C Rando, Thomas A |
| Author_xml | – sequence: 1 givenname: Bérénice A surname: Benayoun fullname: Benayoun, Bérénice A organization: Department of Genetics, Stanford University, Stanford CA 94305, USA; Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford CA 94305, USA – sequence: 2 givenname: Elizabeth A surname: Pollina fullname: Pollina, Elizabeth A organization: Department of Genetics, Stanford University, Stanford CA 94305, USA; Cancer Biology Program, Stanford University, Stanford CA 94305, USA – sequence: 3 givenname: Duygu surname: Ucar fullname: Ucar, Duygu organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 4 givenname: Salah surname: Mahmoudi fullname: Mahmoudi, Salah organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 5 givenname: Kalpana surname: Karra fullname: Karra, Kalpana organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 6 givenname: Edith D surname: Wong fullname: Wong, Edith D organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 7 givenname: Keerthana surname: Devarajan fullname: Devarajan, Keerthana organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 8 givenname: Aaron C surname: Daugherty fullname: Daugherty, Aaron C organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 9 givenname: Anshul B surname: Kundaje fullname: Kundaje, Anshul B organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 10 givenname: Elena surname: Mancini fullname: Mancini, Elena organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 11 givenname: Benjamin C surname: Hitz fullname: Hitz, Benjamin C organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 12 givenname: Rakhi surname: Gupta fullname: Gupta, Rakhi organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 13 givenname: Thomas A surname: Rando fullname: Rando, Thomas A organization: Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford CA 94305, USA; RR&D REAP, VA Palo Alto Health Care Systems, Palo Alto, CA 94304,USA – sequence: 14 givenname: Julie C surname: Baker fullname: Baker, Julie C organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 15 givenname: Michael P surname: Snyder fullname: Snyder, Michael P organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 16 givenname: J Michael surname: Cherry fullname: Cherry, J Michael organization: Department of Genetics, Stanford University, Stanford CA 94305, USA – sequence: 17 givenname: Anne surname: Brunet fullname: Brunet, Anne email: anne.brunet@stanford.edu organization: Department of Genetics, Stanford University, Stanford CA 94305, USA; Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford CA 94305, USA; Cancer Biology Program, Stanford University, Stanford CA 94305, USA. Electronic address: anne.brunet@stanford.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25083876$$D View this record in MEDLINE/PubMed |
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| References | Cell. 2015 Nov 19;163(5):1281-6 |
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| Snippet | Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that... |
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| SubjectTerms | Animals Artificial Intelligence Cells - metabolism Genomics Histone Code Histones - metabolism Humans Lysine - metabolism Methylation Mice, Inbred C57BL Neural Stem Cells - metabolism RNA Polymerase II - metabolism Transcription, Genetic |
| Title | H3K4me3 breadth is linked to cell identity and transcriptional consistency |
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