Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins

Seward, David J.; Cubberley, Gabrielle; Kim, Soojin; Schonewald, Matt; Zhang, Lian; Tripet, Brian; Bentley, David L.

doi:10.1038/nsmb1200

Cited by 160 publications

(128 citation statements)

References 18 publications

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“…For example, the bromodomain reader BRD4, the histone acetyltransferase writer CBP/P300, and the histone deacetylase eraser HDAC2 were especially enriched in the H3K27ac preparation, consistent with their functions at enhancers and promoters (19). The methyltransferase writer ASH2L and the demethylase erasers PHF8, KDM5A, and KDM5B were especially enriched in the H3K4me3 preparation, consistent with their functions in promoter regions (20)(21)(22). The PWWP domain reader N-PAC, an LSD2/KDM1B cofactor that stimulates H3K4 demethylation, was especially enriched in the H3K36me3 preparation (23).…”

Section: Significancementioning

confidence: 50%

Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions

Xiong

Dadon

Abraham

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

120

112

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More than a thousand proteins are thought to contribute to mammalian chromatin and its regulation, but our understanding of the genomic occupancy and function of most of these proteins is limited. Here we describe an approach, which we call "chromatin proteomic profiling," to identify proteins associated with genomic regions marked by specifically modified histones. We used ChIP-MS to identify proteins associated with genomic regions marked by histones modified at specific lysine residues, including H3K27ac, H3K4me3, H3K79me2, H3K36me3, H3K9me3, and H4K20me3, in ES cells. We identified 332 known and 114 novel proteins associated with these histone-marked genomic segments. Many of the novel candidates have been implicated in various diseases, and their chromatin association may provide clues to disease mechanisms. More than 100 histone modifications have been described, so similar chromatin proteomic profiling studies should prove to be valuable for identifying many additional chromatin-associated proteins in a broad spectrum of cell types.chromatin | genomics | proteomics T here are more than 1,000 transcription factors, cofactors, and chromatin regulators encoded in the mammalian genome, but we have limited understanding of the genomic occupancy and function of most of these (1-4). Understanding how these proteins interact with specific active and repressed portions of the genome would provide clues to their functions in global gene control, but limitations inherent in widely used genomic and proteomic technologies make acquiring this information laborious and expensive. Chromatin immunoprecipitation coupled to sequencing (ChIP-seq) can reveal the sites that a specific protein occupies in the genome (5-7) but is laborious and is limited by the availability of antibodies specific to candidate genome-binding proteins. Mass spectrometry (MS) can identify large populations of proteins present in specific preparations (8-10) but does not reveal how these proteins occupy specific portions of the genome. A recently developed approach combined ChIP with MS (ChIP-MS) to identify protein complexes that are associated with other proteins known to occupy sites in the genome (11-13). Here we adapt this approach to profile the proteins associated with chromatin containing specific histone modifications across the genome of mouse embryonic stem cells (mESCs). These chromatin modifications mark regions of the genome where specific transcriptional activities occur, thus implicating the associated proteins in these activities.

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Section: Significancementioning

confidence: 50%

Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions

Xiong

Dadon

Abraham

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

120

112

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“…Our findings explained several inconsistencies observed in previous studies. First, despite being the major H3K4me3 demethylase in yeast, Jhd2 seems unable to demethylate the majority of histones under steady-state conditions (8,10). We now know that because H3K14ac and H3K4me3 are both targeted to the 5′ ends of transcriptionally active genes, K4me3 will often be found on acetylated histone H3 and as a result be protected from the activity of Jhd2.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have identified Jhd2 as a demethylase capable of demethylating H3K4 in vivo (7)(8)(9) and in vitro (10). Although several studies have focused on the identification and substrate specificity of Jhd2, little is known about how it is targeted to specific regions of the genome or how its enzymatic activity is regulated.…”

mentioning

confidence: 99%

Histone H3K4 demethylation is negatively regulated by histone H3 acetylation in Saccharomyces cerevisiae

Maltby¹,

Martin²,

Brind’Amour

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Histone H3 lysine 4 trimethylation (H3K4me3) is a hallmark of transcription initiation, but how H3K4me3 is demethylated during gene repression is poorly understood. Jhd2, a JmjC domain protein, was recently identified as the major H3K4me3 histone demethylase (HDM) in Saccharomyces cerevisiae. Although JHD2 is required for removal of methylation upon gene repression, deletion of JHD2 does not result in increased levels of H3K4me3 in bulk histones, indicating that this HDM is unable to demethylate histones during steady-state conditions. In this study, we showed that this was due to the negative regulation of Jhd2 activity by histone H3 lysine 14 acetylation (H3K14ac), which colocalizes with H3K4me3 across the yeast genome. We demonstrated that loss of the histone H3-specific acetyltransferases (HATs) resulted in genome-wide depletion of H3K4me3, and this was not due to a transcription defect. Moreover, H3K4me3 levels were reestablished in HAT mutants following loss of JHD2, which suggested that H3-specific HATs and Jhd2 serve opposing functions in regulating H3K4me3 levels. We revealed the molecular basis for this suppression by demonstrating that H3K14ac negatively regulated Jhd2 demethylase activity on an acetylated peptide in vitro. These results revealed the existence of a general mechanism for removal of H3K4me3 following gene repression.Gcn5 | histone acetylation | histone methylation | Sas3

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“…Endocrine-Related Cancer (2009) 16 381-389 www.endocrinology-journals.org Klose et al 2007, Lee et al 2007, Ruthenburg et al 2007, Seward et al 2007, Tahiliani et al 2007. Therefore, the methylation state of H3K4 appears to be under tight regulation.…”

Section: Epigenetic Signatures Define Lineagespecific Functional Regumentioning

confidence: 99%

Cistromics of hormone-dependent cancer

Lupien¹,

Brown

2009

Endocrine-Related Cancer

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Alterations in transcription programs are a fundamental feature of cancer. Nuclear receptors, such as the estrogen receptor alpha (ERa) and androgen receptors (ARs), are central in this process as they can directly impact gene expression through interaction with the chromatin and subsequent association with coregulators and the transcriptional machinery. Unbiased genome-wide investigations have demonstrated the predominant recruitment of both ERa and AR to distant (non-promoter)-regulatory elements. Furthermore, these studies revealed a clear relationship between sites of transcription factor recruitment and gene regulation. Indeed, expression profiles from AR-positive primary prostate tumors and cell lines directly relate to the AR cistrome in prostate cancer cells, while the ERa cistrome in breast cancer cells relates to expression profiles from ERa-positive primary breast tumors. Additionally, cell-type-specific ERa cistromes are linked to lineage-specific estrogen-induced expression profiles in different cell types, for example osteosarcoma and breast cancer cells. The pioneer factor forkhead box A1 (FoxA1/HNF3a) plays a central role in AR and ERa signaling. It is recruited in a lineage-specific manner translating the epigenetic signature consisting of mono-and dimethylated histone H3 on lysine 4 (H3K4me1/me2) into functional regulatory elements. Hence, through the interplay between the pioneer factor, namely FoxA1, and epigenetic events, the transcriptional potential of a given cell lineage is predefined. Since this directly impacts signaling through nuclear receptors, these discoveries should significantly impact the development of novel therapeutic strategies directed against multiple types of cancer.

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Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins

Cited by 160 publications

References 18 publications

Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions

Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions

Histone H3K4 demethylation is negatively regulated by histone H3 acetylation in Saccharomyces cerevisiae

Cistromics of hormone-dependent cancer

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