scholarly journals Demethylation of Histone H3K36 and H3K9 by Rph1: a Vestige of an H3K9 Methylation System in Saccharomyces cerevisiae?

2007 ◽  
Vol 27 (11) ◽  
pp. 3951-3961 ◽  
Author(s):  
Robert J. Klose ◽  
Kathryn E. Gardner ◽  
Gaoyang Liang ◽  
Hediye Erdjument-Bromage ◽  
Paul Tempst ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone Methylation ◽  
Budding Yeast ◽  
Large Family ◽  
Epigenetic Inheritance ◽  
Histone Demethylase ◽  
H3k9 Methylation ◽  
Lysine Methylation ◽  
Modification System ◽  
Jmjc Domain

ABSTRACT Histone methylation is an important posttranslational modification that contributes to chromatin-based processes including transcriptional regulation, DNA repair, and epigenetic inheritance. In the budding yeast Saccharomyces cerevisiae, histone lysine methylation occurs on histone H3 lysines 4, 36, and 79, and its deposition is coupled mainly to transcription. Until recently, histone methylation was considered to be irreversible, but the identification of histone demethylase enzymes has revealed that this modification can be dynamically regulated. In budding yeast, there are five proteins that contain the JmjC domain, a signature motif found in a large family of histone demethylases spanning many organisms. One JmjC-domain-containing protein in budding yeast, Jhd1, has recently been identified as being a histone demethylase that targets H3K36 modified in the di- and monomethyl state. Here, we identify a second JmjC-domain-containing histone demethylase, Rph1, which can specifically demethylate H3K36 tri- and dimethyl modification states. Surprisingly, Rph1 can remove H3K9 methylation, a histone modification not found in budding yeast chromatin. The capacity of Rph1 to demethylate H3K9 provides the first indication that S. cerevisiae may have once encoded an H3K9 methylation system and suggests that Rph1 is a functional vestige of this modification system.

scholarly journals The Saccharomyces cerevisiae Histone Demethylase Jhd1 Fine-Tunes the Distribution of H3K36me2

2007 ◽  
Vol 27 (13) ◽  
pp. 5055-5065 ◽  
Author(s):  
Jia Fang ◽  
Gregory J. Hogan ◽  
Gaoyang Liang ◽  
Jason D. Lieb ◽  
Yi Zhang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone Methylation ◽  
Histone Demethylase ◽  
Lysine Methylation ◽  
Chromatin Dynamics ◽  
Histone Lysine Methylation ◽  
Jmjc Domain ◽  
Steady State Levels ◽  
Microarray Studies

ABSTRACT Histone methylation plays important roles in the regulation of chromatin dynamics and transcription. Steady-state levels of histone lysine methylation are regulated by a balance between enzymes that catalyze either the addition or removal of methyl groups. Using an activity-based biochemical approach, we recently uncovered the JmjC domain as an evolutionarily conserved signature motif for histone demethylases. Furthermore, we demonstrated that Jhd1, a JmjC domain-containing protein in Saccharomyces cerevisiae, is an H3K36-specific demethylase. Here we report further characterization of Jhd1. Similar to its mammalian homolog, Jhd1-catalyzed histone demethylation requires iron and α-ketoglutarate as cofactors. Mutation and deletion studies indicate that the JmjC domain and adjacent sequences are critical for Jhd1 enzymatic activity, while the N-terminal PHD domain is dispensable. Overexpression of JHD1 results in a global reduction of H3K36 methylation in vivo. Finally, chromatin immunoprecipitation-coupled microarray studies reveal subtle changes in the distribution of H3K36me2 upon overexpression or deletion of JHD1. Our studies establish Jhd1 as a histone demethylase in budding yeast and suggest that Jhd1 functions to maintain the fidelity of histone methylation patterns along transcription units.

scholarly journals An H3K9 methylation-dependent protein interaction regulates the non-enzymatic functions of a putative histone demethylase

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Gulzhan Raiymbek ◽  
Sojin An ◽  
Nidhi Khurana ◽  
Saarang Gopinath ◽  
Ajay Larkin ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Histone Demethylase ◽  
H3k9 Methylation ◽  
Heterochromatin Formation ◽  
Protein Protein Interaction ◽  
Enzymatic Function ◽  
C Terminus ◽  
Jmjc Domain

H3K9 methylation (H3K9me) specifies the establishment and maintenance of transcriptionally silent epigenetic states or heterochromatin. The enzymatic erasure of histone modifications is widely assumed to be the primary mechanism that reverses epigenetic silencing. Here, we reveal an inversion of this paradigm where a putative histone demethylase Epe1 in fission yeast, has a non-enzymatic function that opposes heterochromatin assembly. Mutations within the putative catalytic JmjC domain of Epe1 disrupt its interaction with Swi6HP1 suggesting that this domain might have other functions besides enzymatic activity. The C-terminus of Epe1 directly interacts with Swi6HP1, and H3K9 methylation stimulates this protein-protein interaction in vitro and in vivo. Expressing the Epe1 C-terminus is sufficient to disrupt heterochromatin by outcompeting the histone deacetylase, Clr3 from sites of heterochromatin formation. Our results underscore how histone modifying proteins that resemble enzymes have non-catalytic functions that regulate the assembly of epigenetic complexes in cells.

scholarly journals The emerging role of KDM5A in human cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guan-Jun Yang ◽  
Ming-Hui Zhu ◽  
Xin-Jiang Lu ◽  
Yan-Jun Liu ◽  
Jian-Fei Lu ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Posttranslational Modification ◽  
Human Cancer ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
Histone Demethylase ◽  
Genome Integrity ◽  
Methyl Groups ◽  
Lysine Specific Demethylase

AbstractHistone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

scholarly journals Hypoxia induces rapid changes to histone methylation and reprograms chromatin

Science ◽  
2019 ◽  
Vol 363 (6432) ◽  
pp. 1222-1226 ◽  
Author(s):  
Michael Batie ◽  
Julianty Frost ◽  
Mark Frost ◽  
James W. Wilson ◽  
Pieta Schofield ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Cultured Cells ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Histone Demethylase ◽  
Histone Demethylases ◽  
Jmjc Domain ◽  
Genomic Locations ◽  
Multicellular Organisms ◽  
Lysine Demethylase

Oxygen is essential for the life of most multicellular organisms. Cells possess enzymes called molecular dioxygenases that depend on oxygen for activity. A subclass of molecular dioxygenases is the histone demethylase enzymes, which are characterized by the presence of a Jumanji-C (JmjC) domain. Hypoxia can alter chromatin, but whether this is a direct effect on JmjC-histone demethylases or due to other mechanisms is unknown. Here, we report that hypoxia induces a rapid and hypoxia-inducible factor–independent induction of histone methylation in a range of human cultured cells. Genomic locations of histone-3 lysine-4 trimethylation (H3K4me3) and H3K36me3 after a brief exposure of cultured cells to hypoxia predict the cell’s transcriptional response several hours later. We show that inactivation of one of the JmjC-containing enzymes, lysine demethylase 5A (KDM5A), mimics hypoxia-induced cellular responses. These results demonstrate that oxygen sensing by chromatin occurs via JmjC-histone demethylase inhibition.

Structure of the JmjC-domain-containing protein JMJD5

2013 ◽  
Vol 69 (10) ◽  
pp. 1911-1920 ◽  
Author(s):  
Haipeng Wang ◽  
Xing Zhou ◽  
Minhao Wu ◽  
Chengliang Wang ◽  
Xiaoqin Zhang ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Embryonic Cell ◽  
Histone Demethylase ◽  
Amino Acid Residues ◽  
Lysine Methylation ◽  
Post Translational Modification ◽  
Active Centre ◽  
Histone Tails ◽  
Demethylase Activity ◽  
Jmjc Domain

The post-translational modification of histone tails is the principal process controlling epigenetic regulation in eukaryotes. The lysine methylation of histones is dynamically regulated by two distinct classes of enzymes: methyltransferases and demethylases. JMJD5, which plays an important role in cell-cycle progression, circadian rhythms and embryonic cell proliferation, has been shown to be a JmjC-domain-containing histone demethylase with enzymatic activity towards H3K36me2. Here, the crystal structure of human JMJD5 lacking the N-terminal 175 amino-acid residues is reported. The structure showed that the Gln275, Trp310 and Trp414 side chains might block the insertion of methylated lysine into the active centre of JMJD5, suppressing the histone demethylase activity of the truncated JMJD5 construct. A comparison of the structure of JMJD5 with that of FIH, a well characterized protein hydroxylase, revealed that human JMJD5 might function as a protein hydroxylase. The interaction between JMJD5 and the core histone octamer proteins indicated that the histone proteins could be potential substrates for JMJD5.

scholarly journals Restricted epigenetic inheritance of H3K9 methylation

Science ◽  
2015 ◽  
Vol 348 (6230) ◽  
pp. 132-135 ◽  
Author(s):  
Pauline N. C. B. Audergon ◽  
Sandra Catania ◽  
Alexander Kagansky ◽  
Pin Tong ◽  
Manu Shukla ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
Histone Demethylase ◽  
Epigenetic Mark ◽  
H3k9 Methylation ◽  
Silent Chromatin ◽  
Wild Type ◽  
Heterochromatin Formation ◽  
Posttranslational Histone Modifications

Posttranslational histone modifications are believed to allow the epigenetic transmission of distinct chromatin states, independently of associated DNA sequences. Histone H3 lysine 9 (H3K9) methylation is essential for heterochromatin formation; however, a demonstration of its epigenetic heritability is lacking. Fission yeast has a single H3K9 methyltransferase, Clr4, that directs all H3K9 methylation and heterochromatin. Using releasable tethered Clr4 reveals that an active process rapidly erases H3K9 methylation from tethering sites in wild-type cells. However, inactivation of the putative histone demethylase Epe1 allows H3K9 methylation and silent chromatin maintenance at the tethering site through many mitotic divisions, and transgenerationally through meiosis, after release of tethered Clr4. Thus, H3K9 methylation is a heritable epigenetic mark whose transmission is usually countered by its active removal, which prevents the unauthorized inheritance of heterochromatin.

scholarly journals Filamentous growth of the budding yeast Saccharomyces cerevisiae induced by overexpression of the WHI2 gene

Microbiology ◽  
1997 ◽  
Vol 143 (6) ◽  
pp. 1867-1876 ◽  
Author(s):  
P. A. Radcliffe ◽  
K. M. Binley ◽  
J. Trevethick ◽  
M. Hall ◽  
P. E. Sudbery
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Budding Yeast ◽  
Filamentous Growth ◽  
Yeast Saccharomyces Cerevisiae
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