Abstract 13917:
            O
            -GlcNAc Levels Are Regulated in a Time and Tissue Specific Manner Independently of Dietary Intake

Background: O -GlcNAcylation ( O -GlcNAc) is a post-translational modification involved in the stress response. A single pair of enzymes, O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA) controls the O -GlcNAcylation. Due to the contribution of energy-linked metabolites (e.g. glucose, glutamine, etc.) to produce UDP-GlcNAc, the substrate used by OGT, O -GlcNAc is considered as a nutrient sensor. Metabolic sources vary from carbohydrates in utero , to fatty acids after birth then a mix once adult. Yet the link between diet composition and O -GlcNAc has never been explored. Purpose: Evaluate changes in O -GlcNAc levels and regulatory mechanisms throughout development. Methods: Organs were harvested from Wistar rats (n=6-8 for each group) before and after birth (D-1 and D0), in suckling animals (D12), after weaning with a standard (D28) or a carbohydrate free diet (D28F), and adult (D84). O -GlcNAc levels and regulatory enzymes were evaluated by Western blots. Mass spectrometry (MS) was performed to quantify known regulators of O -GlcNAc (n=6-8) and identify cardiac O -GlcNAcylated proteins at D0 and D28 (n=2). Results: O -GlcNAc levels fell after birth in the heart, brain and liver (2.5, 1.5 and 1.3-fold, respectively). Interestingly, while O -GlcNAc levels decrease progressively from D0 to D84 (5.75-fold p<0.05) in the heart, the O -GlcNAc changes are opposite and of much smaller magnitude in liver and brain. Regulatory mechanisms appear to be in accordance in heart with a decrease in OGT (4.5-fold; p<0.05), an increase in OGA (125-fold; p<0.05) expression and decrease in UDP-GlcNAc (3-fold; p<0.05) over time. Yet changes in expression of OGT, OGA and UDP-GlcNAc do not follow O -GlcNAc levels in brain and liver. O -GlcNAc levels are unaffected by weaning diet in any tissues. MS analyses identified changes in cardiac levels of specific O -GlcNAcylated proteins, namely those involved in the energy metabolism, such as ACAT1, which is only O -GlcNAcylated at D0. Conclusion: We demonstrate that O -GlcNAc levels are not linked to dietary intake and are regulated in a time and tissue-specific manner during postnatal development. We have identified by MS proteins with a particular O -GlcNAc signature across the development process suggesting specific role for those proteins.

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A comprehensive manually-curated Compendium of Bovine Transcription Factors

10.1101/254011 ◽

2018 ◽

Author(s):

Marcela M de Souza ◽

Juan M Vaquerizas ◽

Adhemar Zerlotini ◽

Ludwig Geistlinger ◽

Benjamín Hernández-Rodríguez ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Regulation Of Gene Expression ◽

Regulatory Proteins ◽

Regulatory Mechanisms ◽

Domain Family ◽

Specific Expression ◽

Tissue Specific ◽

Control Gene Expression ◽

Specific Manner

ABSTRACTTranscription factors (TFs) are pivotal regulatory proteins that control gene expression in a context-dependent and tissue-specific manner. In contrast to human, where comprehensive curated TF collections exist, bovine TFs are only rudimentary recorded and characterized. In this article, we present a manually-curated compendium of 865 sequence-specific DNA-binding bovines TFs, which we analyzed for domain family distribution, evolutionary conservation, and tissue-specific expression. In addition, we provide a list of putative transcription cofactors derived from known interactions with the identified TFs. Since there is a general lack of knowledge concerning the regulation of gene expression in cattle, the curated list of TF should provide a basis for an improved comprehension of regulatory mechanisms that are specific to the species.

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Review of Progress in Predicting Protein Methylation Sites

Current Organic Chemistry ◽

10.2174/1385272823666190723141347 ◽

2019 ◽

Vol 23 (15) ◽

pp. 1663-1670 ◽

Cited By ~ 1

Author(s):

Chunyan Ao ◽

Shunshan Jin ◽

Yuan Lin ◽

Quan Zou

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Transcriptional Activity ◽

Regulation Of Gene Expression ◽

Protein Methylation ◽

Biological Processes ◽

Post Translational Modification ◽

Regulatory Enzymes ◽

Lysine Residues ◽

Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

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Hypertension Increases Connexin43 in a Tissue-Specific Manner

Circulation ◽

10.1161/01.cir.95.4.1007 ◽

1997 ◽

Vol 95 (4) ◽

pp. 1007-1014 ◽

Cited By ~ 59

Author(s):

Jacques-Antoine Haefliger ◽

Einar Castillo ◽

Ge´rard Waeber ◽

Gabriela E. Bergonzelli ◽

Jean-Franc¸ois Aubert ◽

...

Keyword(s):

Tissue Specific ◽

Specific Manner

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The Multifaceted Roles of USP15 in Signal Transduction

International Journal of Molecular Sciences ◽

10.3390/ijms22094728 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4728

Author(s):

Tanuza Das ◽

Eun Joo Song ◽

Eunice EunKyeong Kim

Keyword(s):

Signal Transduction ◽

Signaling Pathways ◽

Cellular Networks ◽

Clinical Applications ◽

Regulatory Mechanisms ◽

Signaling Networks ◽

Post Translational Modification ◽

Comprehensive Overview ◽

E3 Ligases ◽

Disease Markers

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.

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Tentacle Morphological Variation Coincides with Differential Expression of Toxins in Sea Anemones

Toxins ◽

10.3390/toxins13070452 ◽

2021 ◽

Vol 13 (7) ◽

pp. 452

Author(s):

Lauren M. Ashwood ◽

Michela L. Mitchell ◽

Bruno Madio ◽

David A. Hurwood ◽

Glenn F. King ◽

...

Keyword(s):

Differential Expression ◽

Morphological Variation ◽

Expression Profiles ◽

The Body ◽

Sea Anemones ◽

Tissue Specific ◽

Venom Composition ◽

Specific Manner ◽

Branched Structures ◽

Morphological Variants

Phylum Cnidaria is an ancient venomous group defined by the presence of cnidae, specialised organelles that serve as venom delivery systems. The distribution of cnidae across the body plan is linked to regionalisation of venom production, with tissue-specific venom composition observed in multiple actiniarian species. In this study, we assess whether morphological variants of tentacles are associated with distinct toxin expression profiles and investigate the functional significance of specialised tentacular structures. Using five sea anemone species, we analysed differential expression of toxin-like transcripts and found that expression levels differ significantly across tentacular structures when substantial morphological variation is present. Therefore, the differential expression of toxin genes is associated with morphological variation of tentacular structures in a tissue-specific manner. Furthermore, the unique toxin profile of spherical tentacular structures in families Aliciidae and Thalassianthidae indicate that vesicles and nematospheres may function to protect branched structures that host a large number of photosynthetic symbionts. Thus, hosting zooxanthellae may account for the tentacle-specific toxin expression profiles observed in the current study. Overall, specialised tentacular structures serve unique ecological roles and, in order to fulfil their functions, they possess distinct venom cocktails.

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Syntaxin 1A Gene Is Negatively Regulated in a Cell/Tissue Specific Manner by YY1 Transcription Factor, Which Binds to the −183 to −137 Promoter Region Together with Gene Silencing Factors Including Histone Deacetylase

Biomolecules ◽

10.3390/biom11020146 ◽

2021 ◽

Vol 11 (2) ◽

pp. 146

Author(s):

Takahiro Nakayama ◽

Toshiyuki Fukutomi ◽

Yasuo Terao ◽

Kimio Akagawa

Keyword(s):

Transcription Factor ◽

Gene Silencing ◽

Protein Complex ◽

Promoter Region ◽

Neuronal Cell ◽

Syntaxin 1A ◽

Tissue Specific ◽

Cell Tissue ◽

Specific Manner ◽

A Cell

The HPC-1/syntaxin 1A (Stx1a) gene, which is involved in synaptic transmission and neurodevelopmental disorders, is a TATA-less gene with several transcription start sites. It is activated by the binding of Sp1 and acetylated histone H3 to the −204 to +2 core promoter region (CPR) in neuronal cell/tissue. Furthermore, it is depressed by the association of class 1 histone deacetylases (HDACs) to Stx1a–CPR in non-neuronal cell/tissue. To further clarify the factors characterizing Stx1a gene silencing in non-neuronal cell/tissue not expressing Stx1a, we attempted to identify the promoter region forming DNA–protein complex only in non-neuronal cells. Electrophoresis mobility shift assays (EMSA) demonstrated that the −183 to −137 OL2 promoter region forms DNA–protein complex only in non-neuronal fetal rat skin keratinocyte (FRSK) cells which do not express Stx1a. Furthermore, the Yin-Yang 1 (YY1) transcription factor binds to the −183 to −137 promoter region of Stx1a in FRSK cells, as shown by competitive EMSA and supershift assay. Chromatin immunoprecipitation assay revealed that YY1 in vivo associates to Stx1a–CPR in cell/tissue not expressing Stx1a and that trichostatin A treatment in FRSK cells decreases the high-level association of YY1 to Stx1a-CPR in default. Reporter assay indicated that YY1 negatively regulates Stx1a transcription. Finally, mass spectrometry analysis showed that gene silencing factors, including HDAC1, associate onto the −183 to −137 promoter region together with YY1. The current study is the first to report that Stx1a transcription is negatively regulated in a cell/tissue-specific manner by YY1 transcription factor, which binds to the −183 to −137 promoter region together with gene silencing factors, including HDAC.

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Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

International Journal of Molecular Sciences ◽

10.3390/ijms22073463 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3463

Author(s):

Chia-Hung Lin ◽

Chen-Chung Liao ◽

Mei-Yu Chen ◽

Teh-Ying Chou

Keyword(s):

Molecular Mechanisms ◽

Mrna Level ◽

Feedback Regulation ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Cell Physiology ◽

Hydroxyl Groups ◽

Post Translational Modification ◽

Translation Control ◽

Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

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Thiamine Diphosphate Status and Dialysis-Related Losses in End-Stage Kidney Disease Patients Treated with Hemodialysis

Blood Purification ◽

10.1159/000480651 ◽

2017 ◽

Vol 44 (4) ◽

pp. 294-300 ◽

Cited By ~ 5

Author(s):

Magdalena Jankowska ◽

Paweł Rudnicki-Velasquez ◽

Hanna Storoniak ◽

Przemysław Rutkowski ◽

Bolesław Rutkowski ◽

...

Keyword(s):

Body Weight ◽

Kidney Disease ◽

Dietary Intake ◽

Whole Blood ◽

Vitamin B1 ◽

Thiamine Diphosphate ◽

End Stage Kidney Disease ◽

Before And After ◽

End Stage ◽

The Impact

Aim: (1) To describe the whole blood content of thiamine diphosphate (TDP), a biologically active form of vitamin B1 in end-stage kidney disease patients treated with hemodialysis (HD); (2) to establish the impact of a single HD procedure on TDP blood concentrations; and (3) to describe potential explanatory variables influencing TDP dialysis related losses, including dialysis prescription, vitamin B1 dietary intake and supplementation. Methods: Single-center, cross-sectional study in 50 clinically stable maintenance HD patients. The assessment of whole blood TDP with the High Performance Liquid Chromatography method, before and after a single, middle-week dialysis session and analysis of clinical and laboratory parameters potentially influencing TDP status Results: We report a significant difference in TDP levels before and after HD sessions - 42.5 (95% CI 38.7-46.2) μg/L and 23.6 (95% CI 18.9-28.2) μg/L, respectively (p = 0.000). The magnitude of intradialytic TDP changes is highly variable among individuals and is negatively associated only with the body weight of the patients (p < 0.013). Vitamin B1 dietary intake and supplementation do not influence whole blood TDP and dialysis-related loss of TDP. Conclusions: TDP, a bioactive compound of vitamin B1, is substantially lost during the HD procedure, and the magnitude of its loss is associated with the patient's body weight but it is not influenced by vitamin B1 dietary intake and standard supplementation dose.

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Retinoid nutritional status differently affects the expression of Japanese quail retinoic acid receptor-beta isoform transcripts in a tissue-specific manner

Journal of Endocrinology ◽

10.1677/joe.0.1690281 ◽

2001 ◽

Vol 169 (2) ◽

pp. 281-290 ◽

Cited By ~ 3

Author(s):

ZW Fu ◽

T Kubo ◽

K Sugahara ◽

T Noguchi ◽

H Kato

Keyword(s):

Retinoic Acid ◽

Nutritional Status ◽

Japanese Quail ◽

Retinoic Acid Receptor ◽

Mrna Levels ◽

Tissue Specific ◽

Specific Manner ◽

Lower Magnitude ◽

Lung And Kidney ◽

Receptor Beta

We investigated the effects of vitamin A (VA) nutritional status on the levels of expression of retinoic acid (RA) receptor-beta (RARbeta) gene in the various tissues of Japanese quail. VA deficiency caused a significant decrease in the mRNA levels of brain, liver, heart, lung and kidney RARbeta2/beta4, whereas no change was observed in the level of testis RARbeta2 transcript. In contrast, reduction in the RARbeta1 transcript caused by VA depletion was observed only in the lung, remaining unchanged in the other tissues. The administration of RA to the VA-deficient quail rapidly induced the expression of RARbeta2/beta4 mRNAs in all the tissues examined, but RA increased the expression of RARbeta1 transcript in the liver, heart, lung and kidney at a lower magnitude. RA could not change the expression of the brain RARbeta1 transcript, while it induced the expression of the testis RARbeta1 mRNA in a temporal way. These results clearly indicate that VA nutritional status differently regulates the expression of RARbeta1 and RARbeta2/beta4 transcripts in a tissue-specific manner.

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Expression of the genes for the ferritin H and L subunits in rat liver and heart. Evidence for tissue-specific regulations at pre- and post-translational levels

Biochemical Journal ◽

10.1042/bj2750813 ◽

1991 ◽

Vol 275 (3) ◽

pp. 813-816 ◽

Cited By ~ 38

Author(s):

G Cairo ◽

E Rappocciolo ◽

L Tacchini ◽

L Schiaffonati

Keyword(s):

Translational Regulation ◽

Specific Pattern ◽

Regulatory Mechanisms ◽

Mrna Accumulation ◽

Tissue Specific ◽

Protein Levels ◽

Ferritin Gene ◽

Ferritin H ◽

Translational Mechanisms ◽

Different Tissues

The proportion of ferritin light-chain and heavy-chain subunits (L and H) present in the ferritin multimeric shell varies between different tissues. To identify the regulatory mechanisms responsible for the greater amount of L in liver than in heart isoferritins, we analysed ferritin-gene expression at the RNA and protein levels in these two tissues of the rat. In the heart the ratio between the amount of L and H, at the level both of synthesis and accumulation, is about 1 and is the same as the ratio between their respective mRNAs. In contrast, in the liver, the ratio between the L- and H-mRNAs is approx. 2 and cannot entirely explain the large predominance of L in isoferritins in this tissue. Since in the liver the L-mRNA is neither preferentially associated with polyribosomes nor translated more efficiently than its H- counterpart, it seems that the liver-specific isoferritin profile is determined by a combination of pre- and post-translational mechanisms, whereas in heart the post-translational regulation does not seem to be relevant and the tissue-specific pattern is determined at the level of mRNA accumulation.

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