Arabidopsis S2Lb links AtCOMPASS-like and SDG2 activity in histone H3 Lys-4 trimethylation independently from histone H2B monoubiquitination

AbstractThe functional determinants of histone H3 Lys-4 trimethylation (H3K4me3), their potential dependency on histone H2B monoubiquitination (H2Bub) and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike inS. cerevisiae, where a single SET1 protein catalyzes H3 Lys-4 trimethylation as part of COMPASS (COMPlex of proteins ASsociated with Set1), inArabidopsis thalianathis activity involves multiple histone methyltransferases (HMTs). Among these, the plant-specific SDG2 (SET DOMAIN GROUP2) has a prominent role. We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. S2Lb co-purifies with the AtCOMPASS core subunit WDR5 from a high-molecular weight complex, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes.S2Lbknockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. Notwithstanding,s2lbseedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2 or H3 Lys-4 trimethylation, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans-histone crosstalk with histone H2B monoubiquitination. Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been coopted by the plant-specific SDG2 HMT and mediates H3K4me3 deposition through an H2Bub-independent pathway in Arabidopsis.

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The Arabidopsis thaliana genome contains at least 29 active genes encoding SET domain proteins that can be assigned to four evolutionarily conserved classes

Nucleic Acids Research ◽

10.1093/nar/29.21.4319 ◽

2001 ◽

Vol 29 (21) ◽

pp. 4319-4333 ◽

Cited By ~ 196

Author(s):

L. O. Baumbusch

Keyword(s):

Arabidopsis Thaliana ◽

Set Domain ◽

Evolutionarily Conserved ◽

Genes Encoding ◽

Arabidopsis Thaliana Genome ◽

Active Genes

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The N Terminus of Drosophila ESC Binds Directly to Histone H3 and Is Required for E(Z)-Dependent Trimethylation of H3 Lysine 27

Molecular and Cellular Biology ◽

10.1128/mcb.01822-06 ◽

2007 ◽

Vol 27 (6) ◽

pp. 2014-2026 ◽

Cited By ~ 59

Author(s):

Feng Tie ◽

Carl A. Stratton ◽

Rebeccah L. Kurzhals ◽

Peter J. Harte

Keyword(s):

Chromatin Immunoprecipitation ◽

Histone H3 ◽

Polycomb Group ◽

Set Domain ◽

Chromatin Immunoprecipitation Assay ◽

Polycomb Repressive Complex 2 ◽

Polycomb Response Element ◽

Evolutionarily Conserved ◽

Hmtase Activity ◽

And Function

ABSTRACT Polycomb group proteins mediate heritable transcriptional silencing and function through multiprotein complexes that methylate and ubiquitinate histones. The 600-kDa E(Z)/ESC complex, also known as Polycomb repressive complex 2 (PRC2), specifically methylates histone H3 lysine 27 (H3 K27) through the intrinsic histone methyltransferase (HMTase) activity of the E(Z) SET domain. By itself, E(Z) exhibits no detectable HMTase activity and requires ESC for methylation of H3 K27. The molecular basis for this requirement is unknown. ESC binds directly, via its C-terminal WD repeats (β-propeller domain), to E(Z). Here, we show that the N-terminal region of ESC that precedes its β-propeller domain interacts directly with histone H3, thereby physically linking E(Z) to its substrate. We show that when expressed in stable S2 cell lines, an N-terminally truncated ESC (FLAG-ESC61-425), like full-length ESC, is incorporated into complexes with E(Z) and binds to a Ubx Polycomb response element in a chromatin immunoprecipitation assay. However, incorporation of this N-terminally truncated ESC into E(Z) complexes prevents trimethylation of histone H3 by E(Z). We also show that a closely related Drosophila melanogaster paralog of ESC, ESC-like (ESCL), and the mammalian homolog of ESC, EED, also interact with histone H3 via their N termini, indicating that the interaction of ESC with histone H3 is evolutionarily conserved, reflecting its functional importance. Our data suggest that one of the roles of ESC (and ESCL and EED) in PRC2 complexes is to enable E(Z) to utilize histone H3 as a substrate by physically linking enzyme and substrate.

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Structure, Activity and Function of the NSD3 Protein Lysine Methyltransferase

Life ◽

10.3390/life11080726 ◽

2021 ◽

Vol 11 (8) ◽

pp. 726

Author(s):

Philipp Rathert

Keyword(s):

Current Knowledge ◽

Histone H3 ◽

Set Domain ◽

Histone Methyltransferases ◽

Structure Activity ◽

Lysine Methyltransferase ◽

Active Transcription ◽

Biochemical Mechanisms ◽

And Function ◽

Tumor Types

NSD3 is one of six H3K36-specific lysine methyltransferases in metazoans, and the methylation of H3K36 is associated with active transcription. NSD3 is a member of the nuclear receptor-binding SET domain (NSD) family of histone methyltransferases together with NSD1 and NSD2, which generate mono- and dimethylated lysine on histone H3. NSD3 is mutated and hyperactive in some human cancers, but the biochemical mechanisms underlying such dysregulation are barely understood. In this review, the current knowledge of NSD3 is systematically reviewed. Finally, the molecular and functional characteristics of NSD3 in different tumor types according to the current research are summarized.

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Set2-Catalyzed Methylation of Histone H3 Represses Basal Expression of GAL4 in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.23.17.5972-5978.2003 ◽

2003 ◽

Vol 23 (17) ◽

pp. 5972-5978 ◽

Cited By ~ 41

Author(s):

Joseph Landry ◽

Ann Sutton ◽

Tina Hesman ◽

Jinrong Min ◽

Rui-Ming Xu ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Recent Work ◽

Histone Methylation ◽

Histone H3 ◽

Histone Methyltransferases ◽

Basal Expression ◽

Evolutionarily Conserved ◽

Important Regulator

ABSTRACT Recent work has shown that histone methylation is an important regulator of transcription. While much is known about the roles of histone methyltransferases (HMTs) in the establishment of heterochromatin, little is known of their roles in the regulation of actively transcribed genes. We describe an in vivo role of the Saccharomyces cerevisiae HMT, Set2. We identified SET2 as a gene necessary for repression of GAL4 basal expression and show that the evolutionarily conserved SACI, SACII, and SET domains of Set2 are necessary for this repression. We confirm that Set2 catalyzes methylation of lysine 36 on the N-terminal tail of histone H3. Conversion of lysine 36 to an unmethylatable arginine causes a decrease in the repression of GAL4 transcription, as does a Δset2 mutation. We further show that lysine 36 of histone H3 at GAL4 is methylated and that this methylation is dependent upon the presence of SET2.

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Investigation by HPLC of the Catabolism of Recombinant Tissue Plasminogen Activator in the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647645 ◽

1988 ◽

Vol 60 (01) ◽

pp. 107-112 ◽

Cited By ~ 4

Author(s):

Roy Harris ◽

Louis Garcia Frade ◽

Lesley J Creighton ◽

Paul S Gascoine ◽

Maher M Alexandroni ◽

...

Keyword(s):

Molecular Weight ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Half Life ◽

Recombinant Tissue Plasminogen Activator ◽

Rat Plasma ◽

High Molecular Weight Complex ◽

Molecular Weights ◽

Major Activity ◽

Tissue Plasminogen

SummaryThe catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350–500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with Tree t-PA and a complex having a molecular weight of ̴ 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

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Faculty Opinions recommendation of Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1017469.204339 ◽

2004 ◽

Author(s):

Steven Henikoff

Keyword(s):

Histone H3 ◽

Histone H2b

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The Trithorax group protein ASH1 requires a combination of BAH domain and AT hooks, but not the SET domain, for mitotic chromatin binding and survival

Chromosoma ◽

10.1007/s00412-021-00762-z ◽

2021 ◽

Author(s):

Philipp A. Steffen ◽

Christina Altmutter ◽

Eva Dworschak ◽

Sini Junttila ◽

Attila Gyenesei ◽

...

Keyword(s):

Transcriptional Profiling ◽

Histone H3 ◽

Chromatin Binding ◽

Set Domain ◽

Trithorax Group ◽

Trxg Protein ◽

Group Protein ◽

Bah Domain ◽

Mitotic Chromatin

AbstractThe Drosophila Trithorax group (TrxG) protein ASH1 remains associated with mitotic chromatin through mechanisms that are poorly understood. ASH1 dimethylates histone H3 at lysine 36 via its SET domain. Here, we identify domains of the TrxG protein ASH1 that are required for mitotic chromatin attachment in living Drosophila. Quantitative live imaging demonstrates that ASH1 requires AT hooks and the BAH domain but not the SET domain for full chromatin binding in metaphase, and that none of these domains are essential for interphase binding. Genetic experiments show that disruptions of the AT hooks and the BAH domain together, but not deletion of the SET domain alone, are lethal. Transcriptional profiling demonstrates that intact ASH1 AT hooks and the BAH domain are required to maintain expression levels of a specific set of genes, including several involved in cell identity and survival. This study identifies in vivo roles for specific ASH1 domains in mitotic binding, gene regulation, and survival that are distinct from its functions as a histone methyltransferase.

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