Arabidopsis O-GlcNAc transferase SEC activates histone methyltransferase ATX1 to regulate flowering
Ontology highlight
ABSTRACT:
SUBMITTER: Lijing Xing
PROVIDER: S-SCDT-EMBOJ-2017-98115 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Post-translational modification of proteins by O-linked ?-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs). O-GlcNAc modification of proteins regulates multiple important biological processes in metazoans. However, whether protein O-GlcNAcylation is involved in epigenetic processes during plant development is largely unknown. Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype. This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering. SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus. SEC transfers an O-GlcNAc group on Ser947 of ATX1, which resides in the SET domain, thereby activating ATX1. Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
| S-EPMC6166131 | biostudies-literature
Project description:Plants perceive environmental signals such as day length and temperature to determine optimal timing for the transition from vegetative to floral stages. Arabidopsis flowers under long-day conditions through the CONSTANS (CO)-FLOWERING LOCUS T (FT) regulatory module. It is thought that the environmental cues for photoperiodic control of flowering are initially perceived in the leaves. We have previously shown that GIGANTEA (GI) regulates the timing of CO expression, together with FLAVIN-BINDING, KELCH REPEAT, F BOX protein 1. Normally, CO and FT are expressed exclusively in vascular bundles, whereas GI is expressed in various tissues. To better elucidate the role of tissue-specific expression of GI in the flowering pathway, we established transgenic lines in which GI is expressed exclusively in mesophyll, vascular bundles, epidermis, shoot apical meristem, or root. We found that GI expressed in either mesophyll or vascular bundles rescues the late-flowering phenotype of the gi-2 loss-of-function mutant under both short-day and long-day conditions. Interestingly, GI expressed in mesophyll or vascular tissues increases FT expression without up-regulating CO expression under short-day conditions. Furthermore, we examined the interaction between GI and FT repressors in mesophyll. We found that GI can bind to three FT repressors: SHORT VEGETATIVE PHASE (SVP), TEMPRANILLO (TEM)1, and TEM2. Finally, our chromatin immunoprecipitation experiments showed that GI binds to FT promoter regions that are near the SVP binding sites. Taken together, our data further elucidate the multiple roles of GI in the regulation of flowering time.
| S-EPMC3136272 | biostudies-literature
Project description:In this study, we probed the importance of O-GlcNAc transferase (OGT) activity for the survival of tamoxifen-sensitive (TamS) and tamoxifen-resistant (TamR) breast cancer cells. Tamoxifen is an antagonist of estrogen receptor (ERα), a transcription factor expressed in over 50% of breast cancers. ERα-positive breast cancers are successfully treated with tamoxifen; however, a significant number of patients develop tamoxifen-resistant disease. We show that in vitro development of tamoxifen-resistance is associated with increased sensitivity to the OGT small molecule inhibitor OSMI-1. Global transcriptome profiling revealed that TamS cells adapt to OSMI-1 treatment by increasing the expression of histone genes. This is known to mediate chromatin compaction. In contrast, TamR cells respond to OGT inhibition by activating the unfolded protein response and by significantly increasing ERRFI1 expression. ERRFI1 is an endogenous inhibitor of ERBB-signaling, which is a known driver of tamoxifen-resistance. We show that ERRFI1 is selectively downregulated in ERα-positive breast cancers and breast cancers driven by ERBB2. This likely occurs via promoter methylation. Finally, we show that increased ERRFI1 expression is associated with extended survival in patients with ERα-positive tumors (p = 9.2e-8). In summary, we show that tamoxifen-resistance is associated with sensitivity to OSMI-1, and propose that this is explained in part through an epigenetic activation of the tumor-suppressor ERRFI1 in response to OSMI-1 treatment.
| S-EPMC7552408 | biostudies-literature
Project description:Plants have the ability to respond to seasonal environmental variations by monitoring day length to initiate flowering. The transition from vegetative to the reproductive stage is the critical developmental switch in flowering plants to ensure optimal fitness and/or yield. It has been previously reported that B-BOX32 (BBX32) has the potential to increase grain yield when ectopically expressed in soybean. In the present study, we performed a detailed molecular characterization of the Arabidopsis B-box domain gene BBX32 We showed that the circadian clock in Arabidopsis regulates BBX32 and expressed in the early morning. To understand the molecular mechanism of BBX32 regulation, we performed a large-scale yeast two-hybrid screen and identified CONSTANS-LIKE 3 (COL3)/BBX4 as one of its interacting protein partners. Using different genetic and biochemical assays, we have validated this interaction and shown that COL3 targets FT in the presence of BBX32 to regulate the flowering pathway. Based on these findings, we hypothesized that this BBX32-COL3 module could be an additional regulatory mechanism affecting the reproductive development in Arabidopsis that could be translated to crops for increased agricultural productivity.
| S-EPMC5224386 | biostudies-literature
Project description:Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases. The paired-box transcription factor Pax7 is required for satellite cells to generate committed myogenic progenitors. In this study we undertook a multi-level approach to define the role of Pax7 in satellite cell function. Using comparative microarray analysis, we identified several novel and strongly regulated targets; in particular, we identified Myf5 as a gene whose expression was regulated by Pax7. Using siRNA, fluorescence-activated cell sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells. Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7 together with its co-factors. This revealed that Pax7 associates with the Wdr5-Ash2L-MLL2 histone methyltransferase (HMT) complex that directs methylation of histone H3 lysine 4 (H3K4, refs 4-10). Binding of the Pax7-HMT complex to Myf5 resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme.
| S-EPMC2739814 | biostudies-literature
Project description:In this study, we probed the importance of OGT activity for the survival of Tamoxifen-sensitive (TamS) and Tamoxifen-resistant (TamR) breast cancer cells. Tamoxifen is an antagonist of estrogen receptor (ERα), a transcription factor expressed in over half of all breast cancers, and the defining characteristic of the ERα-positive disease. ERα-positive breast cancers are successfully treated with Tamoxifen; however, a significant number of patients develops Tamoxifen-resistant disease. We show here that in vitro development of Tamoxifen-resistance results in acquired sensitivity to OGT small molecule inhibitor OSMI-1. Global transcriptome profiling revealed that TamS cells adapt to OSMI-1 treatment by undergoing significant chromatin compaction. In the TamR cells, however, OGT inhibition induces ERRFI1 tumor-suppressor gene expression. ERRFI1 is an endogenous inhibitor of ERBB-signaling, while activation of the ERBB-signaling is one of the best understood mechanism for Tamoxifen-resistance. We show that ERRFI1 is selectively downregulated in ERα-positive breast cancers and breast cancers driven by ERBB2, and provide data to support that this occurs through promoter methylation. Finally, we show that increased ERRFI1 expression is associated with extended survival in patients with ERα-positive tumors (p=9.2e-8). In summary, we show that Tamoxifen-resistance is associated with acquired sensitivity to OSMI-1, and propose that this is explained in part through an epigenetic activation of the tumor-suppressor ERRFI1 in response to OSMI-1 treatment.
2020-10-22 | GSE148186 | GEO
Project description:Plant flowering is a crucial developmental transition from the vegetative to reproductive phase and is properly timed by a number of intrinsic and environmental cues. Genetic studies have identified that chromatin modification influences the expression of FLOWERING LOCUS C (FLC), a MADS-box transcription factor that controls flowering time. Histone deacetylation and methylation at H3K9 and H3K27 are associated with repression of FLC; in contrast, methylation at H3K4 and H3K36 activates FLC expression. However, little is known about the functions of histone arginine methylation in plants. Here, we report that Arabidopsis Shk1 binding protein 1 (SKB1) catalyzes histone H4R3 symmetric dimethylation (H4R3sme2). SKB1 lesion results in upregulation of FLC and late flowering under both long and short days, but late flowering is reversed by vernalization and gibberellin treatments. An skb1-1flc-3 double mutant blocks late-flowering phenotype, which suggests that SKB1 promotes flowering by suppressing FLC transcription. SKB1 binds to the FLC promoter, and disruption of SKB1 results in reduced H4R3sme2, especially in the promoter of FLC chromatin. Thus, SKB1-mediated H4R3sme2 is a novel histone mark required for repression of FLC expression and flowering time control.
| S-EPMC1847673 | biostudies-literature
Project description:Cytosine methylation of genomic DNA controls gene expression and maintains genome stability. How a specific DNA sequence is targeted for methylation by a methyltransferase is largely unknown. Here, we show that histone H3 tails lacking lysine 4 (K4) methylation function as an allosteric activator for methyltransferase Dnmt3a by binding to its plant homeodomain (PHD). In vitro, histone H3 peptides stimulated the methylation activity of Dnmt3a up to 8-fold, in a manner reversely correlated with the level of K4 methylation. The biological significance of allosteric regulation was manifested by molecular modeling and identification of key residues in both the PHD and the catalytic domain of Dnmt3a whose mutations impaired the stimulation of methylation activity by H3 peptides but not the binding of H3 peptides. Significantly, these mutant Dnmt3a proteins were almost inactive in DNA methylation when expressed in mouse embryonic stem cells while their recruitment to genomic targets was unaltered. We therefore propose a two-step mechanism for de novo DNA methylation - first recruitment of the methyltransferase probably assisted by a chromatin- or DNA-binding factor, and then allosteric activation depending on the interaction between Dnmt3a and the histone tails - the latter might serve as a checkpoint for the methylation activity.
| S-EPMC3193484 | biostudies-literature
Project description:Chromosomal domains in Drosophila are marked by the insulator-binding proteins (IBPs) dCTCF/Beaf32 and cofactors that participate in regulating long-range interactions. Chromosomal borders are further enriched in specific histone modifications, yet the role of histone modifiers and nucleosome dynamics in this context remains largely unknown. Here, we show that IBP depletion impairs nucleosome dynamics specifically at the promoters and coding sequence of genes flanked by IBP binding sites. Biochemical purification identifies the H3K36 histone methyltransferase NSD/dMes-4 as a novel IBP cofactor, which specifically co-regulates the chromatin accessibility of hundreds of genes flanked by dCTCF/Beaf32. NSD/dMes-4 presets chromatin before the recruitment of transcriptional activators including DREF that triggers Set2/Hypb-dependent H3K36 trimethylation, nucleosome positioning, and RNA splicing. Our results unveil a model for how IBPs regulate nucleosome dynamics and gene expression through NSD/dMes-4, which may regulate H3K27me3 spreading. Our data uncover how IBPs dynamically regulate chromatin organization depending on distinct cofactors.
| S-EPMC4198054 | biostudies-literature
Project description:Day length and ambient temperature are major stimuli controlling flowering time. To understand flowering mechanisms in more natural conditions, we explored the effect of daily light and temperature changes on Arabidopsis thaliana. Seedlings were exposed to different day/night temperature and day-length treatments to assess expression changes in flowering genes. Cooler temperature treatments increased CONSTANS (CO) transcript levels at night. Night-time CO induction was diminished in flowering bhlh (fbh)-quadruple mutants. FLOWERING LOCUS T (FT) transcript levels were reduced at dusk, but increased at the end of cooler nights. The dusk suppression, which was alleviated in short vegetative phase (svp) mutants, occurred particularly in younger seedlings, whereas the increase during the night continued over 2 wk. Cooler temperature treatments altered the levels of FLOWERING LOCUS M-β (FLM-β) and FLM-δ splice variants. FT levels correlated strongly with flowering time across treatments. Day/night temperature changes modulate photoperiodic flowering by changing FT accumulation patterns. Cooler night-time temperatures enhance FLOWERING BHLH (FBH)-dependent induction of CO and consequently increase CO protein. When plants are young, cooler temperatures suppress FT at dusk through SHORT VEGETATIVE PHASE (SVP) function, perhaps to suppress precocious flowering. Our results suggest day length and diurnal temperature changes combine to modulate FT and flowering time.
| S-EPMC4887344 | biostudies-literature