scholarly journals BcSas2-Mediated Histone H4K16 Acetylation Is Critical for Virulence and Oxidative Stress Response of Botrytis cinerea

2020 ◽  
Vol 33 (10) ◽  
pp. 1242-1251
Author(s):  
Guangyuan Wang ◽  
Limin Song ◽  
Tingting Bai ◽  
Wenxing Liang
Keyword(s):  
Oxidative Stress ◽  
Botrytis Cinerea ◽  
Target Genes ◽  
Histone Acetyltransferase ◽  
Critical Role ◽  
Rna Seq ◽  
Histone H4 ◽  
Promoter Regions ◽  
Worldwide Distribution ◽  
H4k16 Acetylation

Histone acetyltransferase plays a critical role in transcriptional regulation by increasing accessibility of target genes to transcriptional activators. Botrytis cinerea is an important necrotrophic fungal pathogen with worldwide distribution and a very wide host range, but little is known of how the fungus regulates the transition from saprophytic growth to infectious growth. Here, the function of BcSas2, a histone acetyltransferase of B. cinerea, was investigated. Deletion of the BcSAS2 gene resulted in significantly reduced acetylation levels of histone H4, particularly of H4K16ac. The deletion mutant ΔBcSas2.1 was not only less pathogenic but also more sensitive to oxidative stress than the wild-type strain. RNA-Seq analysis revealed that a total of 13 B. cinerea genes associated with pathogenicity were down-regulated in the ΔBcSas2.1 mutant. Independent knockouts of two of these genes, BcXYGA (xyloglucanase) and BcCAT (catalase), led to dramatically decreased virulence and hypersensitivity to oxidative stress, respectively. Chromatin immunoprecipitation followed by quantitative PCR confirmed that BcSas2 bound directly to the promoter regions of both these pathogenicity-related genes. These observations indicated that BcSas2 regulated the transcription of pathogenicity-related genes by controlling the acetylation level of H4K16, thereby affecting the virulence and oxidative sensitivity of B. cinerea.

scholarly journals Dot1l interacts with Zc3h10 to activate Ucp1 and other thermogenic genes

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Danielle Yi ◽  
Hai P Nguyen ◽  
Jennie Dinh ◽  
Jose A Viscarra ◽  
Ying Xie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Target Genes ◽  
Critical Role ◽  
Direct Interaction ◽  
Fat Cell ◽  
Methyltransferase Activity ◽  
Promoter Regions ◽  
Brown Adipose ◽  
Thermogenic Capacity

Brown adipose tissue is a metabolically beneficial organ capable of dissipating chemical energy into heat, thereby increasing energy expenditure. Here, we identify Dot1l, the only known H3K79 methyltransferase, as an interacting partner of Zc3h10 that transcriptionally activates the Ucp1 promoter and other BAT genes. Through a direct interaction, Dot1l is recruited by Zc3h10 to the promoter regions of thermogenic genes to function as a coactivator by methylating H3K79. We also show that Dot1l is induced during brown fat cell differentiation and by cold exposure and that Dot1l and its H3K79 methyltransferase activity is required for thermogenic gene program. Furthermore, we demonstrate that Dot1l ablation in mice using Ucp1-Cre prevents activation of Ucp1 and other target genes to reduce thermogenic capacity and energy expenditure, promoting adiposity. Hence, Dot1l plays a critical role in the thermogenic program and may present as a future target for obesity therapeutics.

scholarly journals Comparative RNA-Seq analysis reveals a critical role for brassinosteroids in rose (Rosa hybrida) petal defense against Botrytis cinerea infection

BMC Genetics ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Xintong Liu ◽  
Xiaoqian Cao ◽  
Shaochuan Shi ◽  
Na Zhao ◽  
Dandan Li ◽  
...  
Keyword(s):  
Botrytis Cinerea ◽  
Critical Role ◽  
Rosa Hybrida ◽  
Rna Seq

scholarly journals Structure and expression analysis of seven salt-related ERF genes of Populus

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10206
Author(s):  
Juanjuan Huang ◽  
Shengji Wang ◽  
Xingdou Wang ◽  
Yan Fan ◽  
Youzhi Han
Keyword(s):  
Abiotic Stress ◽  
Stress Tolerance ◽  
Expression Pattern ◽  
Target Genes ◽  
Abiotic Stress Tolerance ◽  
Critical Role ◽  
Plant Stress ◽  
Regulation Mechanism ◽  
Rna Seq ◽  
Go Annotation

Ethylene response factors (ERFs) are plant-specific transcription factors (TFs) that play important roles in plant growth and stress defense and have received a great amount of attention in recent years. In this study, seven ERF genes related to abiotic stress tolerance and response were identified in plants of the Populus genus. Systematic bioinformatics, including sequence phylogeny, genome organisation, gene structure, gene ontology (GO) annotation, etc. were detected. Expression-pattern of these seven ERF genes were analyzed using RT-qPCR and cross validated using RNA-Seq. Data from a phylogenetic tree and multiple alignment of protein sequences indicated that these seven ERF TFs belong to three subfamilies and contain AP2, YRG, and RAYD conserved domains, which may interact with downstream target genes to regulate the plant stress response. An analysis of the structure and promoter region of these seven ERF genes showed that they have multiple stress-related motifs and cis-elements, which may play roles in the plant stress-tolerance process through a transcriptional regulation mechanism; moreover, the cellular_component and molecular_function terms associated with these ERFs determined by GO annotation supported this hypothesis. In addition, the spatio-temporal expression pattern of these seven ERFs, as detected using RT-qPCR and RNA-seq, suggested that they play a critical role in mediating the salt response and tolerance in a dynamic and tissue-specific manner. The results of this study provide a solid basis to explore the functions of the stress-related ERF TFs in Populus abiotic stress tolerance and development process.

scholarly journals Dot1L interacts with Zc3h10 to activate UCP1 and other thermogenic genes

2020 ◽  
Author(s):  
Danielle Yi ◽  
Hai P. Nguyen ◽  
Jennie Dinh ◽  
Jose A. Viscarra ◽  
Ying Xie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Target Genes ◽  
Critical Role ◽  
Direct Interaction ◽  
Fat Cell ◽  
Methyltransferase Activity ◽  
Promoter Regions ◽  
Brown Adipose ◽  
Thermogenic Capacity

ABSTRACTBrown adipose tissue is a metabolically beneficial organ capable of dissipating chemical energy into heat, thereby increasing energy expenditure. Here, we identify Dot1L, the only known H3K79 methyltransferase, as an interacting partner of Zc3h10 that transcriptionally activates the UCP1 promoter and other BAT genes. Through a direct interaction, Dot1L is recruited by Zc3h10 to the promoter regions of thermogenic genes to function as a coactivator by methylating H3K79. We also show that Dot1L is induced during brown fat cell differentiation and by cold exposure and that Dot1L and its H3K79 methyltransferase activity is required for thermogenic gene program. Furthermore, we demonstrate that Dot1L ablation in mice using UCP1-Cre prevents activation of UCP1 and other target genes to reduce thermogenic capacity and energy expenditure, promoting adiposity. Hence, Dot1L plays a critical role in the thermogenic program and may present as a future target for obesity therapeutics.

scholarly journals Jun dimerization protein 2 is a critical component of the Nrf2/MafK complex regulating the response to ROS homeostasis

2013 ◽  
Vol 4 (11) ◽  
pp. e921-e921 ◽  
Author(s):  
S Tanigawa ◽  
C H Lee ◽  
C S Lin ◽  
C C Ku ◽  
H Hasegawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Target Genes ◽  
Critical Role ◽  
Notch Receptor ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Mobility Shift ◽  
Basic Leucine Zipper

Abstract Oxidative stress and reactive oxygen species (ROS) are associated with diseases such as cancer, cardiovascular complications, inflammation and neurodegeneration. Cellular defense systems must work constantly to control ROS levels and to prevent their accumulation. We report here that the Jun dimerization protein 2 (JDP2) has a critical role as a cofactor for transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and small Maf protein family K (MafK) in the regulation of the antioxidant-responsive element (ARE) and production of ROS. Chromatin immunoprecipitation–quantitative PCR (qPCR), electrophoresis mobility shift and ARE-driven reporter assays were carried out to examine the role of JDP2 in ROS production. JDP2 bound directly to the ARE core sequence, associated with Nrf2 and MafK (Nrf2–MafK) via basic leucine zipper domains, and increased DNA-binding activity of the Nrf2–MafK complex to the ARE and the transcription of ARE-dependent genes. In mouse embryonic fibroblasts from Jdp2-knockout (Jdp2 KO) mice, the coordinate transcriptional activation of several ARE-containing genes and the ability of Nrf2 to activate expression of target genes were impaired. Moreover, intracellular accumulation of ROS and increased thickness of the epidermis were detected in Jdp2 KO mice in response to oxidative stress-inducing reagents. These data suggest that JDP2 is required to protect against intracellular oxidation, ROS activation and DNA oxidation. qPCR demonstrated that several Nrf2 target genes such as heme oxygenase-1, glutamate–cysteine ligase catalytic and modifier subunits, the notch receptor ligand jagged 1 and NAD(P)H dehydrogenase quinone 1 are also dependent on JDP2 for full expression. Taken together, these results suggest that JDP2 is an integral component of the Nrf2–MafK complex and that it modulates antioxidant and detoxification programs by acting via the ARE.

scholarly journals Cooperation of Dnmt3a R878H with Nras G12D promotes leukemogenesis in knock-in mice: a pilot study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaodong Shi ◽  
Ying Yang ◽  
Siqi Shang ◽  
Songfang Wu ◽  
Weina Zhang ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Morphological Analysis ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Critical Role ◽  
Rna Seq ◽  
Proliferation And Apoptosis ◽  
Blast Cells ◽  
Test Flow ◽  
Genetic Events

Abstract Background DNMT3A R882H, a frequent mutation in acute myeloid leukemia (AML), plays a critical role in malignant hematopoiesis. Recent findings suggest that DNMT3A mutant acts as a founder mutation and requires additional genetic events to induce full-blown AML. Here, we investigated the cooperation of mutant DNMT3A and NRAS in leukemogenesis by generating a double knock-in (DKI) mouse model harboring both Dnmt3a R878H and Nras G12D mutations. Methods DKI mice with both Dnmt3a R878H and Nras G12D mutations were generated by crossing Dnmt3a R878H knock-in (KI) mice and Nras G12D KI mice. Routine blood test, flow cytometry analysis and morphological analysis were performed to determine disease phenotype. RNA-sequencing (RNA-seq), RT-PCR and Western blot were carried out to reveal the molecular mechanism. Results The DKI mice developed a more aggressive AML with a significantly shortened lifespan and higher percentage of blast cells compared with KI mice expressing Dnmt3a or Nras mutation alone. RNA-seq analysis showed that Dnmt3a and Nras mutations collaboratively caused abnormal expression of a series of genes related to differentiation arrest and growth advantage. Myc transcription factor and its target genes related to proliferation and apoptosis were up-regulated, thus contributing to promote the process of leukemogenesis. Conclusion This study showed that cooperation of DNMT3A mutation and NRAS mutation could promote the onset of AML by synergistically disturbing the transcriptional profiling with Myc pathway involvement in DKI mice.

scholarly journals P38α Regulates Expression of DUX4 in Facioscapulohumeral Muscular Dystrophy

2019 ◽  
Author(s):  
L. Alejandro Rojas ◽  
Erin Valentine ◽  
Anthony Accorsi ◽  
Joseph Maglio ◽  
Ning Shen ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Muscle Activation ◽  
Target Genes ◽  
Critical Role ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Rna Seq ◽  
Root Cause ◽  
Expression Activity ◽  
Identification And Characterization

ABSTRACTFSHD is caused by the loss of repression at the D4Z4 locus leading to DUX4 expression in skeletal muscle, activation of its early embryonic transcriptional program and muscle fiber death. While progress toward understanding the signals driving DUX4 expression has been made, the factors and pathways involved in the transcriptional activation of this gene remain largely unknown. Here, we describe the identification and characterization of p38α as a novel regulator of DUX4 expression in FSHD myotubes. By using multiple highly characterized, potent and specific inhibitors of p38α/β, we show a robust reduction of DUX4 expression, activity and cell death across FSHD1 and FSHD2 patient-derived lines. RNA-seq profiling reveals that a small number of genes are differentially expressed upon p38α/β inhibition, the vast majority of which are DUX4 target genes. Our results reveal a novel and apparently critical role for p38α in the aberrant activation of DUX4 in FSHD and support the potential of p38α/β inhibitors as effective therapeutics to treat FSHD at its root cause.VISUAL ABSTRACT

Abstract 17184: Nearly One Third of GWAS CAD Are Putative SMC Klf4 or Oct4 Targets in Advanced Atherosclerotic Lesions

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Gabriel F Alencar ◽  
Ryan Haskins ◽  
Vamsidhar M Venkata ◽  
Johan Bjorkegren ◽  
Stefan Bekiranov ◽  
...  
Keyword(s):  
Target Genes ◽  
Critical Role ◽  
Atherosclerotic Lesion ◽  
Protective Role ◽  
Lineage Tracing ◽  
Rna Seq ◽  
Plaque Instability ◽  
Atherosclerotic Lesions ◽  
Significant Gene ◽  
Migration Pathways

Atherosclerosis is a disease of chronic inflammation and the leading cause of morbidity and mortality worldwide. Despite decades of research, our understanding of the mechanisms regulating plaque stability remains poor. Until recently, smooth muscle cells (SMCs) were thought to play an athero-protective role in lesion pathogenesis. However, rigorous lineage tracing has shown a significant portion (>80%) of SMC-derived cells within an advanced atherosclerotic lesion did not express detectable SMC markers. Furthermore, SMC-specific conditional KO of Klf4 resulted in reduction of several indices of plaque instability and SMC-derived macrophage-like cells. In contrast, conditional KO of Oct4 in SMCs presented a reduction of SMC and increased of Lgals3+ cells within lesions, as well as increase of several indices of plaque instability. Taken together, SMCs can have a beneficial or detrimental effect in lesion pathogenesis. Hypothesis: Combinatorial analysis of Oct4/Klf4 ChIP-seq and RNA-seq of advanced atherosclerotic lesions from our SMC-Klf4 and SMC-Oct4 mice provide a unique opportunity to identify genes that play a critical role in regulating beneficial or detrimental changes in SMC phenotype. Results: SMC-Oct4 target genes are enriched for migration pathways, while SMC-Klf4 target genes are enriched for inflammation pathways. Further, atherosclerosis pathway, among others, presented significant opposite patterns (SMC-Oct4-KO up-regulation and SMC-Klf4-KO down-regulation), and presented strong significant gene anti-correlation, corroborating our phenotypic observations. Remarkably, we cross-reference our ChIP-seq datasets with CAD GWAS and found that 54 of the 161 human loci were either Klf4 and/or Oct4 SMC targets, highly suggesting that CAD GWAS genes might be affecting SMC function in lesion development/pathogenesis. To validate our results, we used the STARNET dataset, and we observed that both Oct4 and Klf4 are significantly up-regulated in aorta of CAD patients compared to controls. In addition, co-expression analysis shows that one of the Klf4 network is highly related to human GWAS CAD, including genes such as LDLR, APOE, PCSK9, TRIB1, and others. Surprisingly, more than 35% of genes in this network also are present in our SMC Klf4 ChIP-seq dataset. Conclusions: our results suggests that: late stage atherosclerotic lesions of mouse and humans seems to be more similar than previously thought; and nearly 1/3 of CAD GWAS loci appear to be affecting SMC function and are potentially Klf4/Oct4-dependent.

scholarly journals Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development

2020 ◽  
Vol 40 (18) ◽  
Author(s):  
Mayank Singh ◽  
Albino Bacolla ◽  
Shilpi Chaudhary ◽  
Clayton R. Hunt ◽  
Shruti Pandita ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Dna Damage Response ◽  
Histone Acetyltransferase ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Development ◽  
Histone H4 ◽  
Kidney Tumors ◽  
Damage Response

ABSTRACT The DNA and protein complex known as chromatin is subject to posttranslational modifications (PTMs) that regulate cellular functions such that PTM dysregulation can lead to disease, including cancer. One critical PTM is acetylation/deacetylation, which is being investigated as a means to develop targeted cancer therapies. The histone acetyltransferase (HAT) family of proteins performs histone acetylation. In humans, MOF (hMOF), a member of the MYST family of HATs, acetylates histone H4 at lysine 16 (H4K16ac). MOF-mediated acetylation plays a critical role in the DNA damage response (DDR) and embryonic stem cell development. Functionally, MOF is found in two distinct complexes: NSL (nonspecific lethal) in humans and MSL (male-specific lethal) in flies. The NSL complex is also able to acetylate additional histone H4 sites. Dysregulation of MOF activity occurs in multiple cancers, including ovarian cancer, medulloblastoma, breast cancer, colorectal cancer, and lung cancer. Bioinformatics analysis of KAT8, the gene encoding hMOF, indicated that it is highly overexpressed in kidney tumors as part of a concerted gene coexpression program that can support high levels of chromosome segregation and cell proliferation. The linkage between MOF and tumor proliferation suggests that there are additional functions of MOF that remain to be discovered.

scholarly journals Genome-wide identification and expression analysis of rice NLR genes responsive to the infections of Xanthomonas oryzae pv. oryzae and Magnaporthe oryzae

2019 ◽  
Author(s):  
Li Ding ◽  
Xiameng Xu ◽  
Weiwen Kong ◽  
Xue Xia ◽  
Shengwei Zhang ◽  
...  
Keyword(s):  
Magnaporthe Oryzae ◽  
Critical Role ◽  
Regulatory Elements ◽  
Xanthomonas Oryzae ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Promoter Regions ◽  
Medium Level ◽  
Rice Disease ◽  
The Veil

Abstract Background Nucleotide-binding site, leucine-rich repeat (NLR) genes play a critical role in rice disease resistance. However, the transcriptional activities of rice NLR genes during pathogen invasions are still unclear.Results To uncover the veil, we identified a total of 430 regular rice NLR genes with both NBS and LRR domains, consisting of 192 CNL and 238 XNL (without a CC motif) members. We performed individual and integrative analyses based on 69 samples from rice microarray after the infections of Xanthomonas oryzae pv. oryzae (Xoo) and Magnaporthe oryzae (Mor). 397 NLR genes were found to be expressed at low/medium level, while 10 NLR genes were observed to show high levels of expression. 400 NLR genes were discovered to be differentially expressed in at least one sample. Further, 46 NLR genes were identified to be differentially expressed in rice response to the two pathogens and 38 of them could be validated by RNA-seq data. Six cis-regulatory elements (MYC, STRE, MYB, ABRE, G-box, and AS-1) were observed to occur frequently in the promoter regions of rice NLR genes. Ten NLR genes were selected for in lab analysis, and qRT-PCR results of seven NLR genes verified the validity of the microarray and RNA-Seq data.Conclusions Our results would shed new light on revealing the roles of NLR genes in rice resistance to Xoo and Mor.

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