scholarly journals Alternative Splicing of Transcription Factors' Genes: Beyond the Increase of Proteome Diversity

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
David Talavera ◽  
Modesto Orozco ◽  
Xavier de la Cruz
Keyword(s):  
Transcription Factors ◽  
Alternative Splicing ◽  
Expression Patterns ◽  
Developmental Changes ◽  
Functional Families ◽  
Transcription Regulators ◽  
Alternatively Spliced ◽  
The Impact ◽  
Human And Mouse

Functional modification of transcription regulators may lead to developmental changes and phenotypical differences between species. In this work, we study the influence of alternative splicing on transcription factors in human and mouse. Our results show that the impact of alternative splicing on transcription factors is similar in both species, meaning that the ways to increase variability should also be similar. However, when looking at the expression patterns of transcription factors, we observe that they tend to diverge regardless of the role of alternative splicing. Finally, we hypothesise that transcription regulation of alternatively spliced transcription factors could play an important role in the phenotypical differences between species, without discarding other phenomena or functional families.

scholarly journals MicroRNA Mediating Networks in Granulosa Cells Associated with Ovarian Follicular Development

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Baoyun Zhang ◽  
Long Chen ◽  
Guangde Feng ◽  
Wei Xiang ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Granulosa Cells ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Follicular Development ◽  
Functional Networks ◽  
Signal Pathways ◽  
Differentially Expressed Mirnas ◽  
Selection Of

Ovaries, which provide a place for follicular development and oocyte maturation, are important organs in female mammals. Follicular development is complicated physiological progress mediated by various regulatory factors including microRNAs (miRNAs). To demonstrate the role of miRNAs in follicular development, this study analyzed the expression patterns of miRNAs in granulosa cells through investigating three previous datasets generated by Illumina miRNA deep sequencing. Furthermore, via bioinformatic analyses, we dissected the associated functional networks of the observed significant miRNAs, in terms of interacting with signal pathways and transcription factors. During the growth and selection of dominant follicles, 15 dysregulated miRNAs and 139 associated pathways were screened out. In comparison of different styles of follicles, 7 commonly abundant miRNAs and 195 pathways, as well as 10 differentially expressed miRNAs and 117 pathways in dominant follicles in comparison with subordinate follicles, were collected. Furthermore, SMAD2 was identified as a hub factor in regulating follicular development. The regulation of miR-26a/b onsmad2messenger RNA has been further testified by real time PCR. In conclusion, we established functional networks which play critical roles in follicular development including pivotal miRNAs, pathways, and transcription factors, which contributed to the further investigation about miRNAs associated with mammalian follicular development.

Role of strain differences on host resistance and the transcriptional response of macrophages to infection withYersinia enterocolitica

2006 ◽  
Vol 25 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Katrin van Erp ◽  
Kristina Dach ◽  
Isabel Koch ◽  
Jürgen Heesemann ◽  
Reinhard Hoffmann
Keyword(s):  
Transcription Factors ◽  
Host Resistance ◽  
Genetic Background ◽  
Antibacterial Properties ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Yersinia Infection ◽  
Ifn Γ ◽  
The Impact

The outcome of a host-pathogen encounter is determined by virulence factors of the pathogen and defense factors of the host. We characterized the impact of host factors [resistant (C57BL/6) or susceptible (BALB/c) genetic background and exposure to interferon (IFN)-γ] on transcriptional responses of bone marrow-derived macrophages (BMDM) to infection with Yersinia enterocolitica. IFN-γ treatment more profoundly altered the transcriptome of BMDM than did bacterial infection or genetic background. In BALB/c BMDM, 1,161 genes were differentially expressed in response to Yersinia infection with or without IFN-γ prestimulation. Fourteen genes (1.2%) could only be induced by BALB/c BMDM in response to Yersinia infection after IFN-γ pretreatment. These genes inhibit apoptosis, activate NF-κB and Erk signaling, are chemotactic to neutrophils, and are involved in cytoskeletal reorganization, hence possibly in phagocytosis. Ten of these genes possess a common module of binding sites for Hox, Pou, and Creb transcription factors in 2 kb of upstream genomic sequence, suggesting a possible novel role of these transcription factors in regulation of immune responses. Fifty-two of one thousand fifty differentially expressed genes (4.9%) were induced more strongly by C57BL/6 BMDM in response to Yersinia infection than BALB/c BMDM. These genes activate NK cells, have antibacterial properties, or are involved in sensing chemokines and lipopolysaccharide (LPS). These data show that host resistance factors modulate a surprisingly small, but identifiable and functionally significant, portion of the macrophage transcriptome in response to Yersinia infection.

scholarly journals Epigenetic regulation of translation repression in ferroptosis, and a role of Alternative splicing and tRNA methylation.

2021 ◽  
Author(s):  
Sherif Rashad ◽  
Daisuke Saigusa ◽  
Yuan Zhou ◽  
Liyin Zhang ◽  
Teiji Tominaga ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Glioma Cells ◽  
Mrna Translation ◽  
Class Ii ◽  
Class I ◽  
Sequencing Analysis ◽  
Translation Repression ◽  
Transsulfuration Pathway ◽  
The Impact

Ferroptosis is a non-apoptotic cell death mechanism characterized by the production of lipid peroxides. Ferroptosis plays important roles in many diseases such as cancer and neurodegenerative diseases. While many effectors in the ferroptosis pathway have been mapped, its epigenetic and epitranscriptional regulatory processes are not yet fully understood. Ferroptosis can be induced via system xCT inhibition (Class I) or GPX4 inhibition (Class II). Previous works have revealed important differences in cellular response to Class I and Class II ferroptosis inducers. Importantly, blocking mRNA transcription or translation appears to protect cells against Class I ferroptosis inducing agents but not Class II. Understanding these subtle differences is important in understanding ferroptosis as well as in developing therapeutics based on ferroptosis for various diseases. In this work, we examined the impact of blocking transcription (via Actinomycin D) or translation (via Cycloheximide) on Erastin (Class I) or RSL3 (Class II) induced ferroptosis. Blocking transcription or translation protected cells against Erastin but was detrimental against RSL3. Cycloheximide led to increased levels of GSH alone or when co-treated with Erastin and the activation of the reverse transsulfuration pathway. RNA sequencing analysis revealed an important and unexplored role of Alternative splicing (AS) in regulating ferroptosis stress response and mRNA translation repression. Our results indicated that translation repression is protective against Erastin but detrimental against RSL3. We tested this theory in Alkbh1 overexpressing glioma cells. Alkbh1 demethylates tRNA and represses translation and is associated with worse outcome in glioma patients. Our results showed that Alkbh1 overexpression protected glioma cells against Erastin but was detrimental against RSL3.

scholarly journals Genome-Wide Analysis Reveals the Potential Role of MYB Transcription Factors in Floral Scent Formation in Hedychium coronarium

2021 ◽  
Vol 12 ◽  
Author(s):  
Farhat Abbas ◽  
Yanguo Ke ◽  
Yiwei Zhou ◽  
Yunyi Yu ◽  
Muhammad Waseem ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Family ◽  
Floral Scent ◽  
Expression Patterns ◽  
Acid Methyl Ester ◽  
Regulatory Elements ◽  
Composition Analysis ◽  
Myb Gene ◽  
Hedychium Coronarium

The MYB gene family is one of the largest groups of transcription factors (TFs) playing diverse roles in several biological processes. Hedychium coronarium (white ginger lily) is a renowned ornamental plant both in tropical and subtropical regions due to its flower shape and strong floral scent mainly composed of terpenes and benzenoids. However, there is no information available regarding the role of the MYB gene family in H. coronarium. In the current study, the MYB gene family was identified and extensively analyzed. The identified 253 HcMYB genes were unevenly mapped on 17 chromosomes at a different density. Promoter sequence analysis showed numerous phytohormones related to cis-regulatory elements. The majority of HcMYB genes contain two to three introns and motif composition analysis showed their functional conservation. Phylogenetic analysis revealed that HcMYBs could be classified into 15 distinct clades, and the segmental duplication events played an essential role in the expansion of the HcMYB gene family. Tissue-specific expression patterns of HcMYB genes displayed spatial and temporal expression. Furthermore, seven HcMYB (HcMYB7/8/75/79/145/238/248) were selected for further investigation. Through RT-qPCR, the response of candidates HcMYB genes toward jasmonic acid methyl ester (MeJA), abscisic acid (ABA), ethylene, and auxin was examined. Yeast one-hybrid (Y1H) assays revealed that candidate genes directly bind to the promoter of bottom structural volatile synthesis genes (HcTPS1, HcTPS3, HcTPS10, and HcBSMT2). Moreover, yeast two-hybrid (Y2H) assay showed that HcMYB7/8/75/145/248 interact with HcJAZ1 protein. In HcMYB7/8/79/145/248-silenced flowers, the floral volatile contents were decreased and downregulated the expression of key structural genes, suggesting that these genes might play crucial roles in floral scent formation in H. coronarium by regulating the expression of floral scent biosynthesis genes. Collectively, these findings indicate that HcMYB genes might be involved in the regulatory mechanism of terpenoids and benzenoid biosynthesis in H. coronarium.

Mechanisms of Transcriptional Regulation and Transformation by HOXA9

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-30-SCI-30
Author(s):  
Jay L. Hess ◽  
Cailin Collins ◽  
Joel Bronstein ◽  
Yuqing Sun ◽  
Surya Nagaraja
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Target Genes ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
A Genome ◽  
The Impact

Abstract Abstract SCI-30 HOXA9 plays important roles in both development and hematopoiesis and is overexpressed in more than 50 percent of acute myeloid leukemias (AML). Nearly all cases of AML with mixed lineage leukemia (MLL) translocations show increased HOXA9 expression, as well as cases with mutation of the nucleophosmin gene NPM1, overexpression of CDX2, and fusions of NUP98. In most cases, upregulation of HOXA9 is accompanied by upregulation of its homeodomain-containing cofactor MEIS1, which directly interacts with HOXA9. While HOXA9 alone is sufficient for transformation of hematopoietic stem cells in culture, the addition of MEIS1 increases the transformation efficiency and results in rapidly fatal leukemias in transplanted animals. Despite the crucial role that HOXA9 plays in development, hematopoiesis, and leukemia, its transcriptional targets and mechanisms of action are poorly understood. We have used ChIP-seq to identify Hoxa9 and Meis1 binding sites on a genome-wide level in myeloblastic cells, profiled their associated epigenetic modifications, identified the target genes regulated by HOXA9 and identified HOXA9 interacting proteins. HOXA9 and MEIS1 cobind at hundreds of promoter distal, highly evolutionarily conserved sites showing high levels of histone H3K4 monomethylation and CBP/P300 binding. These include many proleukemogenic gene loci, such as Erg, Flt3, Myb, Lmo2, and Sox4. In addition, HOXA9 binding sites overlap a subset of enhancers previously implicated in myeloid differentiation and inflammation. HOXA9 binding at enhancers stabilizes association of MEIS1 and lineage-restricted transcription factors, including C/EBPα, PU.1, and STAT5A/B thereby promoting CBP/p300 recruitment, histone acetylation, and transcriptional activation. Current efforts are focused on using both biochemical and genetic approaches to assess the role of HOXA9 “enhanceosome” components C/EBPα, PU.1, and STAT5A/B in transcriptional regulation and leukemogenesis. Studies to date suggest that C/EBPα and PU.1 binding can occur in the absence of HOXA9/MEIS1, supporting a model in which these proteins act as pioneer transcription factors for establishment of poised, but not activated, HOXA9-regulated enhancers. Work is under way to assess the impact of high-level HOXA9 and MEIS1 on enhanceosome assembly and the role of recruitment of transcriptional coactivators involved in target gene up- or downregulation, including histone acetyltransferases and chromatin remodeling complexes. Collectively, our findings suggest that HOXA9-regulated enhancers are a fundamental mechanism of HOX-mediated transcription in normal development that is deregulated in leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Probing the Honey Bee Diet-Microbiota-Host Axis Using Pollen Restriction and Organic Acid Feeding

Insects ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 291
Author(s):  
Vincent A. Ricigliano ◽  
Kirk E. Anderson
Keyword(s):  
Organic Acid ◽  
Honey Bee ◽  
Expression Patterns ◽  
Feeding Behaviors ◽  
Fermentation Products ◽  
Bacterial Fermentation ◽  
Bee Health ◽  
Gene Transcripts ◽  
The Impact

Microbial metabolites are considered important drivers of diet-based microbiota influence on the host, however, mechanistic models are confounded by interactions between diet, microbiota function, and host physiology. The honey bee harbors a simple microbiota that produces organic acids as fermentation products of dietary nectar and pollen, making it a model for gut microbiota research. Herein, we demonstrate that bacterial abundance in the honey bee gut is partially associated with the anterior rectum epithelium. We used dietary pollen restriction and organic acid feeding treatments to obtain information about the role of undigested pollen as a microbiota growth substrate and the impact of bacterial fermentation products on honey bee enteroendocrine signaling. Pollen restriction markedly reduced total and specific bacterial 16S rRNA abundance in the anterior rectum but not in the ileum. Anterior rectum expression levels of bacterial fermentative enzyme gene transcripts (acetate kinase, lactate dehydrogenase, and hydroxybutyryl-CoA dehydrogenase) were reduced in association with diet-induced microbiota shifts. To evaluate the effects of fermentative metabolites on host enteroendocrine function, pollen-restricted bees were fed an equimolar mixture of organic acid sodium salts (acetate, lactate, butyrate, formate, and succinate). Organic acid feeding significantly impacted hindgut enteroendocrine signaling gene expression, rescuing some effects of pollen restriction. This was specifically manifested by tissue-dependent expression patterns of neuropeptide F and allatostatin pathways, which are implicated in energy metabolism and feeding behaviors. Our findings provide new insights into the diet-microbiota-host axis in honey bees and may inform future efforts to improve bee health through diet-based microbiota manipulations.

scholarly journals Role of FoxO Proteins in Cellular Response to Antitumor Agents

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 90 ◽  
Author(s):  
Giovanni Luca Beretta ◽  
Cristina Corno ◽  
Nadia Zaffaroni ◽  
Paola Perego
Keyword(s):  
Drug Resistance ◽  
Transcription Factors ◽  
Cellular Response ◽  
Antitumor Agents ◽  
Antitumor Agent ◽  
Dna Interaction ◽  
Nuclear Retention ◽  
Induced Apoptosis ◽  
The Impact

FoxO proteins (FoxOs) are transcription factors with a common DNA binding domain that confers selectivity for DNA interaction. In human cells, four proteins (FoxO1, FoxO3, FoxO4 and FoxO6), with redundant activity, exhibit mainly a positive effect on genes involved in cell cycle, apoptosis regulation and drug resistance. Thus, FoxOs can affect cell response to antitumor agent treatment. Their transcriptional activity depends on post-translational modifications, including phosphorylation, acetylation, and mono/poly-ubiquitination. Additionally, alterations in microRNA network impact on FoxO transcripts and in turn on FoxO levels. Reduced expression of FoxO1 has been associated with resistance to conventional agents (e.g., cisplatin) and with reduced efficacy of drug combinations in ovarian carcinoma cells. FoxO3 has been shown as a mediator of cisplatin toxicity in colorectal cancer. A requirement for FoxO3-induced apoptosis has been reported in cells exposed to targeted agents (e.g., gefitinib). Recently, the possibility to interfere with FoxO1 localization has been proposed as a valuable approach to improve cell sensitivity to cisplatin, because nuclear retention of FoxO1 may favor the induction of pro-apoptotic genes. This review focuses on the role of FoxOs in drug treatment response in tumor cells and discusses the impact of the expression of these transcription factors on drug resistance/sensitivity.

scholarly journals Evolutionary conservation of the structure and expression of alternatively spliced Ultrabithorax isoforms from Drosophila.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 965-977
Author(s):  
H M Bomze ◽  
A J López
Keyword(s):  
Alternative Splicing ◽  
Protein Function ◽  
Developmental Regulation ◽  
Expression Patterns ◽  
Proximal Region ◽  
Amino Acid Sequences ◽  
Drosophila Virilis ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
Alternatively Spliced

Abstract In Drosophila melanogaster, alternatively spliced mRNAs from the homeotic gene Ultrabithorax (Ubx) encode a family of structurally distinct homeoprotein isoforms. The developmentally regulated expression patterns of these isoforms suggest that they have specialized stage- and tissue-specific functions. To evaluate the functional importance of UBX isoform diversity and gain clues to the mechanism that regulates processing of Ubx RNAs, we have investigated whether the Ubx RNAs of other insects undergo similar alternative splicing. We have isolated and characterized Ubx cDNA fragments from D. melanogaster, Drosophila pseudoobscura, Drosophila hydei and Drosophila virilis, species separated by as much as 60 million years of evolution, and have found that three aspects of Ubx RNA processing have been conserved. (1) These four species exhibit identical patterns of optional exon use in a region adjacent to the homeodomain. (2) These four species produce the same family of UBX protein isoforms with identical amino acid sequences in the optional exons, even though the common amino-proximal region has undergone substantial divergence. The nucleotide sequences of the optional exons, including third positions of rare codons, have also been conserved strongly, suggesting functional constraints that are not limited to coding potential. (3) The tissue- and stage-specific patterns of expression of different UBX isoforms are identical among these Drosophila species, indicating that the developmental regulation of the alternative splicing events has also been conserved. These findings argue for an important role of alternative splicing in Ubx function. We discuss the implications of these results for models of UBX protein function and the mechanism of alternative splicing.

scholarly journals Evidence for the role of transcription factors in the co-transcriptional regulation of intron retention

2021 ◽  
Author(s):  
Fahad Ullah ◽  
Maayan Salton ◽  
Anireddy S.N. Reddy ◽  
Asa Ben-Hur
Keyword(s):  
Transcription Factors ◽  
Alternative Splicing ◽  
Zinc Finger ◽  
Intron Retention ◽  
Single Gene ◽  
Open Chromatin ◽  
Multiple Transcripts ◽  
High Prevalence ◽  
Retained Introns

Alternative splicing is a widespread regulatory phenomenon that enables a single gene to produce multiple transcripts. Among the different types of alternative splicing, intron retention is one of the least explored despite its high prevalence in both plants and animals. The recent discovery that the majority of splicing is co-transcriptional has led to the finding that chromatin state affects alternative splicing. Therefore it is plausible that transcription factors can regulate splicing outcomes. We provide evidence for this hypothesis by studying regions of open chromatin in retained and excised introns. Using deep learning models designed to distinguish between regions of open chromatin in retained introns and non-retained introns, we identified motifs enriched in IR events with significant hits to known human transcription factors. Our model predicts that the majority of transcription factors that affect intron retention come from the zinc finger family. We demonstrate the validity of these predictions using ChIP-seq data for multiple zinc finger transcription factors and find strong over-representation for their peaks in intron retention events. Availability: Source code available at https://github.com/fahadahaf/chromir

Identification of Variants of ISL1 Gene Promoter and Cellular Functions in Isolated Ventricular Septal Defects

2021 ◽  
Author(s):  
Si-Qiang Zheng ◽  
Huan-Xin Chen ◽  
Xiao-Cheng Liu ◽  
Qin Yang ◽  
Guo-Wei He
Keyword(s):  
Transcription Factors ◽  
Promoter Region ◽  
Gene Promoter ◽  
Chinese Patients ◽  
Luciferase Reporter ◽  
Ventricular Septal Defects ◽  
Septal Defects ◽  
The Impact ◽  
Gene Promoter Region

Ventricular septal defects (VSD) are the most common congenital heart defects (CHD). Studies have documented that ISL1 has a crucial impact on cardiac growth, but the role of variants in the ISL1 gene promoter in patients with VSD has not been explored. In 400 subjects (200 isolated and sporadic VSD patients: 200 healthy controls), we investigated the ISL1 gene promoter variant and performed cellular functional experiments by using the dual-luciferase reporter assay to verify the impact on gene expression. In the ISL1 promoter, 5 variants were found only in VSD patients by sequencing. Cellular functional experiments demonstrated that three variants decreased the transcriptional activity of the ISL1 promoter (P < 0.05). Further analysis with the online JASPAR database demonstrated that a cluster of putative binding sites for transcription factors may be altered by these variants, possibly resulting in change of ISL1 protein expression and VSD formation. Our study has for the first time identified novel variants in the ISL1 gene promoter region in the Han Chinese patients with isolated and sporadic VSD. Additionally, the cellular functional experiments, electrophoretic mobility shift assay, and bioinformatic analysis have demonstrated that these variants significantly alter the expression of the ISL1 gene and affect the binding of transcription factors, likely resulting in VSD. Therefore, this study may provide new insights into the role of the gene promoter region for a better understanding of genetic basis of the formation of CHD and may promote further investigations on mechanism of the formation of CHD.

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