Histone H4 Lysine 20 (H4K20) Methylation, Expanding the Signaling Potential of the Proteome One Methyl Moiety at a Time

Nuland, Rick van; Gozani, Or

doi:10.1074/mcp.r115.054742

Cited by 59 publications

(54 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both peptides contain lysines K16 and K20. The mono-, di- and trimethylated states of K20 are well known (Van Nuland and Gozani, 2016), while K16 is known to be acetylated, and was only recently found to be also methylated in a comprehensive mass spectrometry study (Tan et al, 2011). K20 methylation states are catalyzed by different enzymes with SETD8 known to be a monomethyltransferase for H4K20 and SUV420H1/2 acting as K20 di- and trimethyltransferases (Beck et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

“…While H3K27me3 and H3K9me2/3 marks have been linked to HIV-1 latency and have known ties to heterochromatin formation, an association of H4K20me1 with HIV-1 latency was initially surprising. H4K20me1/2 are involved in DNA replication and DNA damage repair, whereas H4K20me3 is a mark of silenced heterochromatic regions (Van Nuland and Gozani, 2016). However, H4K20me1 regulates cell-cycle progression where its levels decline during G1 phase, resulting in very low levels of H4K20me1 in the beginning of S phase.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency

Boehm

Jeng

Camus

et al. 2017

Cell Host & Microbe

View full text Add to dashboard Cite

Summary Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin-remodeling complexes and post-translational histone modifications likely play key roles in HIV-1 reactivation but the underlying mechanisms are incompletely understood. We performed a RNAi-based screen of human lysine methyltransferases and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological inhibition reactivated latent HIV-1 in T-cell lines and in primary CD4+ T cells. SMYD2 associated with latent HIV-1 promoter chromatin, which was enriched in monomethylated lysine 20 at histone H4 (H4K20me1), a mark lost in cells lacking SMYD2. Further, we find that lethal 3 malignant brain tumor 1 (L3MBTL1), a reader protein with chromatin-compacting properties that recognizes H4K20me1, was recruited to the latent HIV-1 promoter in a SMYD2-dependent manner. We propose that a SMYD2-H4K20me1-L3MBTL1 axis contributes to HIV-1 latency and can be targeted with small-molecule SMYD2 inhibitors.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency

Boehm

Jeng

Camus

et al. 2017

Cell Host & Microbe

View full text Add to dashboard Cite

show abstract

“…Lysine 20 is the predominant methylation site on H4, and this modification is important for development in higher eukaryotes (reviewed in [59]). H4K20 methylation is associated with regulating transcription, the DNA damage response, and cell cycle progression [59].…”

Section: Discussionmentioning

confidence: 99%

Histone peptide microarray screen of chromo and Tudor domains defines new histone lysine methylation interactions

Shanle

Shinsky

Bridgers

et al. 2017

Epigenetics & Chromatin

View full text Add to dashboard Cite

BackgroundHistone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized “reader” domains. Despite efforts to elucidate reader domain–PTM interactions, the influence of neighboring PTMs and the target specificity of many reader domains is still unclear. The aim of this study was to use a high-throughput histone peptide microarray platform to interrogate 83 known and putative histone reader domains from the chromo and Tudor domain families to identify their interactions and characterize the influence of neighboring PTMs on these interactions. ResultsNearly a quarter of the chromo and Tudor domains screened showed interactions with histone PTMs by peptide microarray, revealing known and several novel methyllysine interactions. Specifically, we found that the CBX/HP1 chromodomains that recognize H3K9me also recognize H3K23me2/3—a poorly understood histone PTM. We also observed that, in addition to their interaction with H3K4me3, Tudor domains of the Spindlin family also recognized H4K20me3—a previously uncharacterized interaction. Several Tudor domains also showed novel interactions with H3K4me as well.ConclusionsThese results provide an important resource for the epigenetics and chromatin community on the interactions of many human chromo and Tudor domains. They also provide the basis for additional studies into the functional significance of the novel interactions that were discovered.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-017-0117-5) contains supplementary material, which is available to authorized users.

show abstract

“…H4K20Me 1 concentrations are the highest in the G 2 /M phase, gradually decline during the G 1 phase, and remain very low throughout the S phase (Rice et al., 2002, Beck et al., 2012b, van Nuland and Gozani, 2016). This correlates with the similar cell-cycle-dependent changes in Kmt5a (also known as Setd8 or PR-Set7) protein levels, the sole enzyme catalyzing H4K20Me 1 .…”

Section: Introductionmentioning

confidence: 99%

Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions

et al. 2017

View full text Add to dashboard Cite

SummaryH4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. Here, we show that, in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted in an energy starvation condition partially compensated by AMP-activated protein kinase (AMPK) activation and increased mitochondrial activity. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage. The results illustrate how defects in the general process of RNA Pol II transition into a productive elongation phase can trigger specific metabolic changes and genome instability.

show abstract

Histone H4 Lysine 20 (H4K20) Methylation, Expanding the Signaling Potential of the Proteome One Methyl Moiety at a Time

Cited by 59 publications

References 90 publications

SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency

SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency

Histone peptide microarray screen of chromo and Tudor domains defines new histone lysine methylation interactions

Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions

Contact Info

Product

Resources

About