scholarly journals Pbx1 Represses Osteoblastogenesis by Blocking Hoxa10-Mediated Recruitment of Chromatin Remodeling Factors

2010 ◽  
Vol 30 (14) ◽  
pp. 3531-3541 ◽  
Author(s):  
Jonathan A. R. Gordon ◽  
Mohammad Q. Hassan ◽  
Sharanjot Saini ◽  
Martin Montecino ◽  
Andre J. van Wijnen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylases ◽  
Skeletal Development ◽  
Regulation Of Gene Expression ◽  
Gene Activation ◽  
Gene Promoters ◽  
Homeodomain Proteins ◽  
Temporal Regulation ◽  
Multipotent Cells ◽  
P300 Recruitment

ABSTRACT Abdominal-class homeodomain-containing (Hox) factors form multimeric complexes with TALE-class homeodomain proteins (Pbx, Meis) to regulate tissue morphogenesis and skeletal development. Here we have established that Pbx1 negatively regulates Hoxa10-mediated gene transcription in mesenchymal cells and identified components of a Pbx1 complex associated with genes in osteoblasts. Expression of Pbx1 impaired osteogenic commitment of C3H10T1/2 multipotent cells and differentiation of MC3T3-E1 preosteoblasts. Conversely, targeted depletion of Pbx1 by short hairpin RNA (shRNA) increased expression of osteoblast-related genes. Studies using wild-type and mutated osteocalcin and Bsp promoters revealed that Pbx1 acts through a Pbx-binding site that is required to attenuate gene activation by Hoxa10. Chromatin-associated Pbx1 and Hoxa10 were present at osteoblast-related gene promoters preceding gene expression, but only Hoxa10 was associated with these promoters during transcription. Our results show that Pbx1 is associated with histone deacetylases normally linked with chromatin inactivation. Loss of Pbx1 from osteoblast promoters in differentiated osteoblasts was associated with increased histone acetylation and CBP/p300 recruitment, as well as decreased H3K9 methylation. We propose that Pbx1 plays a central role in attenuating the ability of Hoxa10 to activate osteoblast-related genes in order to establish temporal regulation of gene expression during osteogenesis.

scholarly journals Temporal Regulation of Gene Expression of the Escherichia coli Bacteriophage phiEco32

2012 ◽  
Vol 416 (3) ◽  
pp. 389-399 ◽  
Author(s):  
Olga Pavlova ◽  
Daria Lavysh ◽  
Evgeny Klimuk ◽  
Marko Djordjevic ◽  
Dmitry A. Ravcheev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Regulation Of Gene Expression ◽  
Temporal Regulation

scholarly journals Food Bioactive HDAC Inhibitors in the Epigenetic Regulation of Heart Failure

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1120 ◽  
Author(s):  
Levi Evans ◽  
Bradley Ferguson
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Drug Efficacy ◽  
Histone Deacetylation ◽  
Epigenetic Modifiers

Approximately 5.7 million U.S. adults have been diagnosed with heart failure (HF). More concerning is that one in nine U.S. deaths included HF as a contributing cause. Current HF drugs (e.g., β-blockers, ACEi) target intracellular signaling cascades downstream of cell surface receptors to prevent cardiac pump dysfunction. However, these drugs fail to target other redundant intracellular signaling pathways and, therefore, limit drug efficacy. As such, it has been postulated that compounds designed to target shared downstream mediators of these signaling pathways would be more efficacious for the treatment of HF. Histone deacetylation has been linked as a key pathogenetic element for the development of HF. Lysine residues undergo diverse and reversible post-translational modifications that include acetylation and have historically been studied as epigenetic modifiers of histone tails within chromatin that provide an important mechanism for regulating gene expression. Of recent, bioactive compounds within our diet have been linked to the regulation of gene expression, in part, through regulation of the epi-genome. It has been reported that food bioactives regulate histone acetylation via direct regulation of writer (histone acetyl transferases, HATs) and eraser (histone deacetylases, HDACs) proteins. Therefore, bioactive food compounds offer unique therapeutic strategies as epigenetic modifiers of heart failure. This review will highlight food bio-actives as modifiers of histone deacetylase activity in the heart.

Homeodomain proteins and the regulation of gene expression

1990 ◽  
Vol 2 (3) ◽  
pp. 485-495 ◽  
Author(s):  
M. Affolter ◽  
A. Schier ◽  
W.J. Gehring
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Homeodomain Proteins

Meta-analysis of transcriptome data identified TGTCNN motif variants associated with the response to plant hormone auxin in Arabidopsis thaliana L.

2016 ◽  
Vol 14 (02) ◽  
pp. 1641009 ◽  
Author(s):  
Elena V. Zemlyanskaya ◽  
Daniil S. Wiebe ◽  
Nadezhda A. Omelyanchuk ◽  
Victor G. Levitsky ◽  
Victoria V. Mironova
Keyword(s):  
Gene Expression ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Gene Promoters ◽  
Auxin Response ◽  
Regulatory Regions ◽  
Core Motif ◽  
Functional Roles ◽  
Functional Features ◽  
Time Specific

Auxin is the major regulator of plant growth and development. It regulates gene expression via a family of transcription factors (ARFs) that bind to auxin responsive elements (AuxREs) in the gene promoters. The canonical AuxREs found in regulatory regions of many auxin responsive genes contain the TGTCTC core motif, whereas ARF binding site is a degenerate TGTCNN with TGTCGG strongly preferred. Thereby two questions arise: which TGTCNN variants are functional AuxRE cores and whether different TGTCNN variants have distinct functional roles? In this study, we performed meta-analysis of microarray data to reveal TGTCNN variants essential for auxin response and to characterize their functional features. Our results indicate that four TGTCNN motifs (TGTCTC, TGTCCC, TGTCGG, and TGTCTG) are associated with auxin up-regulation and two (TGTCGG, TGTCAT) with auxin down-regulation, but to a lesser extent. The genes having some of these motifs in their regulatory regions showed time-specific auxin response. Functional annotation of auxin up- and down-regulated genes also revealed GO terms specific for the auxin-regulated genes with certain TGTCNN variants in their promoters. Our results provide an idea that various TGTCNN motifs may play distinct roles in the auxin regulation of gene expression.

scholarly journals Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5

Science ◽  
2021 ◽  
Vol 372 (6546) ◽  
pp. 1085-1091
Author(s):  
Débora R. Sobreira ◽  
Amelia C. Joslin ◽  
Qi Zhang ◽  
Iain Williamson ◽  
Grace T. Hansen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Genomic Region ◽  
Metabolic Effects ◽  
Allelic Heterogeneity ◽  
Temporal Regulation ◽  
Regulatory Effects ◽  
Specific Tissue ◽  
Coding Variants ◽  
Regulatory Properties

Whereas coding variants often have pleiotropic effects across multiple tissues, noncoding variants are thought to mediate their phenotypic effects by specific tissue and temporal regulation of gene expression. Here, we investigated the genetic and functional architecture of a genomic region within the FTO gene that is strongly associated with obesity risk. We show that multiple variants on a common haplotype modify the regulatory properties of several enhancers targeting IRX3 and IRX5 from megabase distances. We demonstrate that these enhancers affect gene expression in multiple tissues, including adipose and brain, and impart regulatory effects during a restricted temporal window. Our data indicate that the genetic architecture of disease-associated loci may involve extensive pleiotropy, allelic heterogeneity, shared allelic effects across tissues, and temporally restricted effects.

scholarly journals Peptide Regulation of Gene Expression: A Systematic Review

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7053
Author(s):  
Vladimir Khatskelevich Khavinson ◽  
Irina Grigor’evna Popovich ◽  
Natalia Sergeevna Linkova ◽  
Ekaterina Sergeevna Mironova ◽  
Anastasiia Romanovna Ilina
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
Short Peptides ◽  
Gene Promoters ◽  
Amino Acid Residues ◽  
Sequence Recognition ◽  
Wide Range ◽  
The Status ◽  
Synthetic Reactions

Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such action of peptides involves their ability to regulate gene expression and protein synthesis in plants, microorganisms, insects, birds, rodents, primates, and humans. Short peptides, consisting of 2–7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA. DNA–peptide interactions, including sequence recognition in gene promoters, are important for template-directed synthetic reactions, replication, transcription, and reparation. Peptides can regulate the status of DNA methylation, which is an epigenetic mechanism for the activation or repression of genes in both the normal condition, as well as in cases of pathology and senescence. In this context, one can assume that short peptides were evolutionarily among the first signaling molecules that regulated the reactions of template-directed syntheses. This situation enhances the prospects of developing effective and safe immunoregulatory, neuroprotective, antimicrobial, antiviral, and other drugs based on short peptides.

Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update

2020 ◽  
Vol 26 (40) ◽  
pp. 7212-7280 ◽  
Author(s):  
Faria Sultana ◽  
Kesari Lakshmi Manasa ◽  
Siddiq Pasha Shaik ◽  
Srinivasa Reddy Bonam ◽  
Ahmed Kamal
Keyword(s):  
Gene Expression ◽  
Drug Therapy ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Rational Drug Design ◽  
Combination Drug Therapy ◽  
Combination Drug

Background: Histone deacetylases (HDAC) are an important class of enzymes that play a pivotal role in epigenetic regulation of gene expression that modifies the terminal of core histones leading to remodelling of chromatin topology and thereby controlling gene expression. HDAC inhibitors (HDACi) counter this action and can result in hyperacetylation of histones, thereby inducing an array of cellular consequences such as activation of apoptotic pathways, generation of reactive oxygen species (ROS), cell cycle arrest and autophagy. Hence, there is a growing interest in the potential clinical use of HDAC inhibitors as a new class of targeted cancer therapeutics. Methodology and Result: Several research articles spanning between 2016 and 2017 were reviewed in this article and presently offer critical insights into the important strategies such as structure-based rational drug design, multi-parameter lead optimization methodologies, relevant SAR studies and biology of various class of HDAC inhibitors, such as hydroxamic acids, benzamides, cyclic peptides, aliphatic acids, summarising the clinical trials and results of various combination drug therapy till date. Conclusion: This review will provide a platform to the synthetic chemists and biologists to cater the needs of both molecular targeted therapy and combination drug therapy to design and synthesize safe and selective HDAC inhibitors in cancer therapeutics.

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