Production and action of interferons: New insights into molecular mechanisms of gene regulation and expression

1994 ◽  
pp. 239-270
Author(s):  
Mark P. Hayes ◽  
Kathryn C. Zoon
Keyword(s):  
Gene Regulation ◽  
Molecular Mechanisms

scholarly journals Novel Gene Regulation in Normal and Abnormal Spermatogenesis

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 666
Author(s):  
Li Du ◽  
Wei Chen ◽  
Zixin Cheng ◽  
Si Wu ◽  
Jian He ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Leydig Cells ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
Genetic Regulation ◽  
Myoid Cells ◽  
Epigenetic Factors ◽  
Future Directions ◽  
New Genes ◽  
Human Spermatogenesis

Spermatogenesis is a complex and dynamic process which is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulating the normal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubular myoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.

scholarly journals Dysregulation of NRSF/REST via EHMT1 is associated with psychiatric disorders

2021 ◽  
Author(s):  
Mouhamed Alsaqati ◽  
Brittany A Davis ◽  
Jamie Wood ◽  
Megan Jones ◽  
Lora Jones ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Psychiatric Disorders ◽  
Molecular Mechanisms ◽  
Neurodevelopmental Disorder ◽  
Mirna Gene ◽  
Neuronal Gene ◽  
Kleefstra Syndrome ◽  
Elevated Expression ◽  
H3k9 Dimethylation ◽  
Human Ipsc

SummaryGenetic evidence indicates disrupted epigenetic regulation as a major risk factor for psychiatric disorders, but the molecular mechanisms that drive this association are undetermined. EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a neurodevelopmental disorder (NDD) leading to ID, and is associated with schizophrenia. Here, we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. We further show that EHMT1 regulates NRSF/REST indirectly via repression of miRNA leading to aberrant neuronal gene regulation and neurodevelopment timing. Expression of a NRSF/REST mRNA that lacks the miRNA-binding sites restores neuronal gene regulation to EHMT1 deficient cells. Importantly, the EHMT1-regulated miRNA gene set with elevated expression is enriched for NRSF/REST regulators with an association for ID and schizophrenia. This reveals a molecular interaction between H3K9 dimethylation and NSRF/REST contributing to the aetiology of psychiatric disorders.

scholarly journals Common genetic risk variants identified in the SPARK cohort implicate DDHD2 as a novel autism risk gene

2020 ◽  
Author(s):  
Nana Matoba ◽  
Dan Liang ◽  
Huaigu Sun ◽  
Nil Aygün ◽  
Jessica C. McAfee ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Association Study ◽  
Genetic Risk ◽  
Molecular Mechanisms ◽  
Autism Spectrum ◽  
Risk Variants ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Gene Regulatory

AbstractBackgroundAutism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder. Large genetically informative cohorts of individuals with ASD have led to the identification of three common genome-wide significant (GWS) risk loci to date. However, many more common genetic variants are expected to contribute to ASD risk given the high heritability. Here, we performed a genome-wide association study (GWAS) using the Simons Foundation Powering Autism Research for Knowledge (SPARK) dataset to identify additional common genetic risk factors and molecular mechanisms underlying risk for ASD.MethodsWe performed an association study on 6,222 case-pseudocontrol pairs from SPARK and meta-analyzed with a previous GWAS. We integrated gene regulatory annotations to map non-coding risk variants to their regulated genes. Further, we performed a massively parallel reporter assay (MPRA) to identify causal variant(s) within a novel risk locus.ResultsWe identified one novel GWS locus from the SPARK GWAS. The meta-analysis identified four significant loci, including an additional novel locus. We observed significant enrichment of ASD heritability within regulatory regions of the developing cortex, indicating that disruption of gene regulation during neurodevelopment is critical for ASD risk. The MPRA identified one variant at the novel locus with strong impacts on gene regulation (rs7001340), and expression quantitative trait loci data demonstrated an association between the risk allele and decreased expression of DDHD2 (DDHD domain containing 2) in both adult and pre-natal brains.ConclusionsBy integrating genetic association data with multi-omic gene regulatory annotations and experimental validation, we fine-mapped a causal risk variant and demonstrated that DDHD2 is a novel gene associated with ASD risk.

Transcription in Living Cells: Molecular Mechanisms of Bursting

2020 ◽  
Vol 89 (1) ◽  
pp. 189-212 ◽  
Author(s):  
Joseph Rodriguez ◽  
Daniel R. Larson
Keyword(s):  
Gene Regulation ◽  
Rna Synthesis ◽  
Molecular Mechanisms ◽  
Gene Activation ◽  
Living Cells ◽  
Single Locus ◽  
Individual Gene ◽  
Technological Advances ◽  
Transcriptional Bursting ◽  
Cell Data

Transcription in several organisms from certain bacteria to humans has been observed to be stochastic in nature: toggling between active and inactive states. Periods of active nascent RNA synthesis known as bursts represent individual gene activation events in which multiple polymerases are initiated. Therefore, bursting is the single locus illustration of both gene activation and repression. Although transcriptional bursting was originally observed decades ago, only recently have technological advances enabled the field to begin elucidating gene regulation at the single-locus level. In this review, we focus on how biochemical, genomic, and single-cell data describe the regulatory steps of transcriptional bursts.

scholarly journals The molecular mechanisms of Foxp3 gene regulation

2011 ◽  
Vol 23 (6) ◽  
pp. 418-423 ◽  
Author(s):  
Takashi Maruyama ◽  
Joanne E. Konkel ◽  
Brian F. Zamarron ◽  
WanJun Chen
Keyword(s):  
Gene Regulation ◽  
Molecular Mechanisms ◽  
Foxp3 Gene

scholarly journals Sensing, Signaling, and Secretion: A Review and Analysis of Systems for Regulating Host Interaction in Wolbachia

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 813 ◽  
Author(s):  
Amelia R. I. Lindsey
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Promising Candidate ◽  
Regulate Gene Expression ◽  
Host Interaction ◽  
Female Germline ◽  
Intracellular Infections ◽  
Regulate Gene

Wolbachia (Anaplasmataceae) is an endosymbiont of arthropods and nematodes that resides within host cells and is well known for manipulating host biology to facilitate transmission via the female germline. The effects Wolbachia has on host physiology, combined with reproductive manipulations, make this bacterium a promising candidate for use in biological- and vector-control. While it is becoming increasingly clear that Wolbachia’s effects on host biology are numerous and vary according to the host and the environment, we know very little about the molecular mechanisms behind Wolbachia’s interactions with its host. Here, I analyze 29 Wolbachia genomes for the presence of systems that are likely central to the ability of Wolbachia to respond to and interface with its host, including proteins for sensing, signaling, gene regulation, and secretion. Second, I review conditions under which Wolbachia alters gene expression in response to changes in its environment and discuss other instances where we might hypothesize Wolbachia to regulate gene expression. Findings will direct mechanistic investigations into gene regulation and host-interaction that will deepen our understanding of intracellular infections and enhance applied management efforts that leverage Wolbachia.

scholarly journals Promoter-Proximal Chromatin Domain Insulator Protein BEAF Mediates Local and Long-Range Communication with a Transcription Factor and Directly Activates a Housekeeping Promoter in Drosophila

Genetics ◽  
2020 ◽  
Vol 215 (1) ◽  
pp. 89-101 ◽  
Author(s):  
Yuankai Dong ◽  
S. V. Satya Prakash Avva ◽  
Mukesh Maharjan ◽  
Janice Jacobi ◽  
Craig M. Hart
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Housekeeping Genes ◽  
Bimolecular Fluorescence Complementation ◽  
Chromatin Domain ◽  
Direct Role ◽  
Transcription Start Sites ◽  
Genome Wide

BEAF (Boundary Element-Associated Factor) was originally identified as a Drosophila melanogaster chromatin domain insulator-binding protein, suggesting a role in gene regulation through chromatin organization and dynamics. Genome-wide mapping found that BEAF usually binds near transcription start sites, often of housekeeping genes, suggesting a role in promoter function. This would be a nontraditional role for an insulator-binding protein. To gain insight into molecular mechanisms of BEAF function, we identified interacting proteins using yeast two-hybrid assays. Here, we focus on the transcription factor Serendipity δ (Sry-δ). Interactions were confirmed in pull-down experiments using bacterially expressed proteins, by bimolecular fluorescence complementation, and in a genetic assay in transgenic flies. Sry-δ interacted with promoter-proximal BEAF both when bound to DNA adjacent to BEAF or > 2-kb upstream to activate a reporter gene in transient transfection experiments. The interaction between BEAF and Sry-δ was detected using both a minimal developmental promoter (y) and a housekeeping promoter (RpS12), while BEAF alone strongly activated the housekeeping promoter. These two functions for BEAF implicate it in playing a direct role in gene regulation at hundreds of BEAF-associated promoters.

LDL stimulates collagen mRNA synthesis in mesangial cells through induction of PKC and TGF-β expression

1999 ◽  
Vol 277 (3) ◽  
pp. F369-F376 ◽  
Author(s):  
Hyun Soon Lee ◽  
Bong Cho Kim ◽  
Hye Kyung Hong ◽  
Young Sook Kim
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Density Lipoprotein ◽  
Collagen Gene ◽  
Collagen Mrna ◽  
Collagen Gene Expression

Abnormal lipid accumulation in glomeruli could be implicated in the pathogenesis of glomerulosclerosis. Low-density lipoprotein (LDL) stimulates collagen mRNA expression in cultured human mesangial cells (HMC). To explore the possible molecular mechanisms by which LDL promotes collagen gene expression, we examined the effects of LDL on protein kinase C (PKC) activity and transforming growth factor-β (TGF-β) expression in relation to collagen gene regulation in HMC. LDL (200 μg/ml) induced an acute increase in PKC activity, particularly PKC-α and -δ, within 15 min, which decreased to control value at 2 h. LDL stimulated TGF-β1, and α1(I) and α1(IV) collagen mRNA expression within 30 min of incubation with HMC, and levels remained elevated until hour 4. LDL induced the secretion of TGF-β by HMC. This TGF-β was shown by CCL-64 mink lung cell assay to be, in part, bioactive. The stimulatory effects of LDL on collagen gene regulation in HMC were blocked by the inhibition of PKC using GF-109203X (GFX) or the downregulation of PKC using phorbol myristate acetate. Neutralizing antibody to TGF-β inhibited the increased collagen mRNA expression by HMC exposed to LDL. The downregulation or inhibition of PKC did not affect the stimulatory effect of LDL on TGF-β mRNA or protein expression. These results suggest that in HMC, LDL stimulates collagen mRNA expression through the rapid activation of PKC-α and -δ and transcriptional upregulation of TGF-β. Thus PKC and TGF-β may function as independent key signaling intermediaries in the pathway by which LDL upregulates collagen gene expression in HMC.

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