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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Vydáno v:	Cell Ročník 158; číslo 3; s. 673
Hlavní autoři:	Benayoun, Bérénice A, Pollina, Elizabeth A, Ucar, Duygu, Mahmoudi, Salah, Karra, Kalpana, Wong, Edith D, Devarajan, Keerthana, Daugherty, Aaron C, Kundaje, Anshul B, Mancini, Elena, Hitz, Benjamin C, Gupta, Rakhi, Rando, Thomas A, Baker, Julie C, Snyder, Michael P, Cherry, J Michael, Brunet, Anne
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 31.07.2014
Témata:	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
ISSN:	1097-4172, 1097-4172
On-line přístup:	Zjistit podrobnosti o přístupu
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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.
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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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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