scholarly journals Set4 coordinates the activity of histone deacetylases and regulates stress-responsive gene expression within subtelomeric regions in yeast

2021 ◽  
Author(s):  
Yogita Jethmalani ◽  
Khoa Tran ◽  
Deepika Jaiswal ◽  
Meagan Jezek ◽  
Mark Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Global Gene Expression ◽  
Growth Conditions ◽  
Stress Response Genes ◽  
Hypoxic Conditions ◽  
Sir Complex ◽  
Stress Dependent

The yeast chromatin protein Set4 is a member of the Set3-subfamily of SET domain proteins which play critical roles in the regulation of gene expression in diverse developmental and environmental contexts, although they appear to lack methyltransferase activity. The molecular functions of Set4 are relatively unexplored, likely due to its low abundance in standard growth conditions. We previously reported that Set4 promotes survival during oxidative stress and regulates expression of stress response genes via stress-dependent chromatin localization. In this study, global gene expression analysis and investigation of histone modification status has revealed a role for Set4 in maintaining gene repressive mechanisms within yeast subtelomeres under both normal and stress conditions. We show that Set4 works in a partially overlapping pathway to the SIR complex and the histone deacetylase Rpd3 to maintain proper levels of histone acetylation and expression of stress response genes encoded in subtelomeres. This role for Set4 is particularly critical for cells under hypoxic conditions, and the loss of Set4 decreases cell fitness and cell wall integrity in hypoxia. These findings uncover a new regulator of subtelomeric chromatin that is key to stress defense pathways and demonstrate a function for yeast Set4 in regulating repressive, heterochromatin-like environments.

scholarly journals Set4 regulates stress response genes and coordinates histone deacetylases within yeast subtelomeres

2021 ◽  
Vol 4 (12) ◽  
pp. e202101126
Author(s):  
Yogita Jethmalani ◽  
Khoa Tran ◽  
Maraki Y Negesse ◽  
Winny Sun ◽  
Mark Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Global Gene Expression ◽  
Stress Response Genes ◽  
Hypoxic Conditions ◽  
Global Gene Expression Analysis ◽  
Sir Complex ◽  
Stress Dependent

The yeast chromatin protein Set4 is a member of the Set3-subfamily of SET domain proteins which play critical roles in the regulation of gene expression in diverse developmental and environmental contexts. We previously reported that Set4 promotes survival during oxidative stress and regulates expression of stress response genes via stress-dependent chromatin localization. In this study, global gene expression analysis and investigation of histone modification status identified a role for Set4 in maintaining gene repressive mechanisms within yeast subtelomeres under both normal and stress conditions. We show that Set4 works in a partially overlapping pathway to the SIR complex and the histone deacetylase Rpd3 to maintain proper levels of histone acetylation and expression of stress response genes encoded in subtelomeres. This role for Set4 is particularly critical for cells under hypoxic conditions, where the loss of Set4 decreases cell fitness and cell wall integrity. These findings uncover a new regulator of subtelomeric chromatin that is key to stress defense pathways and demonstrate a function for Set4 in regulating repressive, heterochromatin-like environments.

scholarly journals Global Gene Expression Responses of Fission Yeast to Ionizing Radiation

2004 ◽  
Vol 15 (2) ◽  
pp. 851-860 ◽  
Author(s):  
Adam Watson ◽  
Juan Mata ◽  
Jürg Bähler ◽  
Anthony Carr ◽  
Tim Humphrey
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Stress Response ◽  
Ionizing Radiation ◽  
Environmental Stress ◽  
Fission Yeast ◽  
Transcriptional Response ◽  
Global Gene Expression ◽  
Environmental Stress Response ◽  
Stress Response Genes

A coordinated transcriptional response to DNA-damaging agents is required to maintain genome stability. We have examined the global gene expression responses of the fission yeast Schizosaccharomyces pombe to ionizing radiation (IR) by using DNA microarrays. We identified ∼200 genes whose transcript levels were significantly altered at least twofold in response to 500 Gy of gamma IR in a temporally defined manner. The majority of induced genes were core environmental stress response genes, whereas the remaining genes define a transcriptional response to DNA damage in fission yeast. Surprisingly, few DNA repair and checkpoint genes were transcriptionally modulated in response to IR. We define a role for the stress-activated mitogen-activated protein kinase Sty1/Spc1 and the DNA damage checkpoint kinase Rad3 in regulating core environmental stress response genes and IR-specific response genes, both independently and in concert. These findings suggest a complex network of regulatory pathways coordinate gene expression responses to IR in eukaryotes.

scholarly journals Global gene expression patterns in response to white patch syndrome: Disentangling symbiont loss from the thermal stress response in reef-building coral

2019 ◽  
Author(s):  
Carly D. Kenkel ◽  
Veronique J.L. Mocellin ◽  
Line K. Bay
Keyword(s):  
Gene Expression ◽  
Abiotic Stress ◽  
Thermal Stress ◽  
Stress Response ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Host Protein ◽  
Gene Expression Patterns ◽  
White Patch

AbstractThe mechanisms resulting in the breakdown of the coral symbiosis once the process of bleaching has been initiated remain unclear. Distinguishing symbiont loss from the abiotic stress response may shed light on the cellular and molecular pathways involved in each process. This study examined physiological changes and global gene expression patterns associated with white patch syndrome (WPS) in P. lobata, which manifests in localized bleaching independent of thermal stress. In addition, a meta-analysis of global gene expression studies in other corals and anemones was used to contrast differential regulation as a result of abiotic stress from expression patterns correlated with symbiotic state. Symbiont density, chlorophyll a content, holobiont productivity, instant calcification rate, and total host protein content were uniformly reduced in WPS relative to healthy tissue. While expression patterns associated with WPS were secondary to fixed effects of source colony, specific functional enrichments suggest that the viral infection putatively giving rise to this condition affects symbiont rather than host cells. The meta-analysis revealed that expression patterns in WPS-affected tissues were significantly correlated with prior studies examining short-term thermal stress responses. This correlation was independent of symbiotic state, as the strongest correlations were found between WPS adults and both symbiotic adult and aposymbiotic coral larvae experiencing thermal stress, suggesting that the majority of expression changes reflect a non-specific stress response. Across studies, the magnitude and direction of expression change among particular functional enrichments suggests unique responses to stressor duration, and highlights unique responses to bleaching in an anemone model which engages in a non-obligate symbiosis.

scholarly journals Role of Sigma Factors in Controlling Global Gene Expression in Light/Dark Transitions in the Cyanobacterium Synechocystis sp. Strain PCC 6803

2007 ◽  
Vol 189 (21) ◽  
pp. 7829-7840 ◽  
Author(s):  
Tina C. Summerfield ◽  
Louis A. Sherman
Keyword(s):  
Gene Expression ◽  
Global Gene Expression ◽  
Growth Conditions ◽  
Day Length ◽  
Regulation Of Transcription ◽  
Wild Type ◽  
Protein Levels ◽  
In The Wild ◽  
Altered Gene ◽  
Pcc 6803

ABSTRACT We report on differential gene expression in the cyanobacterium Synechocystis sp. strain PCC 6803 after light-dark transitions in wild-type, ΔsigB, and ΔsigD strains. We also studied the effect of day length in the presence of glucose on a ΔsigB ΔsigE mutant. Our results indicated that the absence of SigB or SigD predominately altered gene expression in the dark or in the light, respectively. In the light, approximately 350 genes displayed transcript levels in the ΔsigD strain that were different from those of the wild type, with over 200 of these up-regulated in the mutant. In the dark, removal of SigB altered more than 150 genes, and the levels of 136 of these were increased in the mutant compared to those in the wild type. The removal of both SigB and SigE had a major impact on gene expression under mixotrophic growth conditions and resulted in the inability of cells to grow in the presence of glucose with 8-h light and 16-h dark cycles. Our results indicated the importance of group II σ factors in the global regulation of transcription in this organism and are best explained by using the σ cycle paradigm with the stochastic release model described previously (R. A. Mooney, S. A. Darst, and R. Landick, Mol. Cell 20:335-345, 2005). We combined our results with the total protein levels of the σ factors in the light and dark as calculated previously (S. Imamura, S. Yoshihara, S. Nakano, N. Shiozaki, A. Yamada, K. Tanaka, H. Takahashi, M. Asayama, and M. Shirai, J. Mol. Biol. 325:857-872, 2003; S. Imamura, M. Asayama, H. Takahashi, K. Tanaka, H. Takahashi, and M. Shirai, FEBS Lett. 554:357-362, 2003). Thus, we concluded that the control of global transcription is based on the amount of the various σ factors present and able to bind RNA polymerase.

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.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document