Developmental gene expression profiles of the human pathogen Schistosoma japonicum

AbstractChemical modifications of proteins, DNA and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3’ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 hours starting from 72 hours post-fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (FDR 5%), respectively. The majority of the peaks were preferentially located around the 3’UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (e.g., ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, foxi1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

Download Full-text

Developmental gene expression differences between humans and mammalian models

10.1101/747782 ◽

2019 ◽

Cited By ~ 2

Author(s):

Margarida Cardoso-Moreira ◽

Britta Velten ◽

Matthew Mort ◽

David N. Cooper ◽

Wolfgang Huber ◽

...

Keyword(s):

Gene Expression ◽

Human Gene ◽

Expression Profiles ◽

Mammalian Species ◽

Disease Genes ◽

Organ Development ◽

Developmental Gene ◽

Human Organ ◽

Developmental Gene Expression ◽

Human Genes

AbstractIdentifying the molecular programs underlying human organ development and how they differ from those in model species will advance our understanding of human health and disease. Developmental gene expression profiles provide a window into the genes underlying organ development as well as a direct means to compare them across species. We use a transcriptomic resource for mammalian organ development to characterize the temporal profiles of human genes associated with distinct disease classes and to determine, for each human gene, the similarity of its spatiotemporal expression with its orthologs in rhesus macaque, mouse, rat and rabbit. We find that half of human genes differ from their mouse orthologs in their temporal trajectories. These include more than 200 disease genes associated with brain, heart and liver disease, for which mouse models should undergo extra scrutiny. We provide a new resource that evaluates for every human gene its suitability to be modeled in different mammalian species.

Download Full-text

PCB126 Exposure Revealed Alterations in m6A RNA Modifications in Transcripts Associated With AHR Activation

Toxicological Sciences ◽

10.1093/toxsci/kfaa158 ◽

2020 ◽

Cited By ~ 1

Author(s):

Neelakanteswar Aluru ◽

Sibel I Karchner

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Profiles ◽

Chemical Exposure ◽

Environmental Chemicals ◽

Rna Modifications ◽

Environmental Chemical ◽

Stop Codons ◽

Developmental Gene Expression

Abstract Chemical modifications of proteins, DNA, and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests the RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3′ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 h starting from 72 h post fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (false discovery rate 5%), respectively. The majority of the peaks were preferentially located around the 3′ UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (eg, ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, sned1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

Download Full-text

Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00202.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. E298-E307 ◽

Cited By ~ 233

Author(s):

Tamara Tchkonia ◽

Marc Lenburg ◽

Thomas Thomou ◽

Nino Giorgadze ◽

Garrett Frampton ◽

...

Keyword(s):

Expression Profiles ◽

Gene Expression Profiles ◽

Pcr Analysis ◽

Homeotic Genes ◽

Developmental Gene ◽

Fat Cell ◽

Developmental Gene Expression ◽

Fat Depots ◽

The Metabolic Syndrome ◽

Population Doublings

Anatomically separate fat depots differ in size, function, and contribution to pathological states, such as the metabolic syndrome. We isolated preadipocytes from different human fat depots to determine whether the basis for this variation is partly attributable to differences in inherent properties of fat cell progenitors. We found that genome-wide expression profiles of primary preadipocytes cultured in parallel from abdominal subcutaneous, mesenteric, and omental fat depots were distinct. Interestingly, visceral fat was not homogeneous. Preadipocytes from one of the two main visceral depots, mesenteric fat, had an expression profile closer to that of subcutaneous than omental preadipocytes, the other main visceral depot. Expression of genes that regulate early development, including homeotic genes, differed extensively among undifferentiated preadipocytes isolated from different fat depots. These profiles were confirmed by real-time PCR analysis of preadipocytes from additional lean and obese male and female subjects. We made preadipocyte strains from single abdominal subcutaneous and omental preadipocytes by expressing telomerase. Depot-specific developmental gene expression profiles persisted for 40 population doublings in these strains. Thus, human fat cell progenitors from different regions are effectively distinct, consistent with different fat depots being separate mini-organs.

Download Full-text

Exposure of neonatal mice to bromine impairs their alveolar development and lung function

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00315.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. L137-L143 ◽

Cited By ~ 14

Author(s):

Tamas Jilling ◽

Changchun Ren ◽

Aaron Yee ◽

Saurabh Aggarwal ◽

Brian Halloran ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Smooth Muscle Actin ◽

Gene Expression Profiles ◽

Global Gene Expression ◽

Lung Compliance ◽

Inhalation Injury ◽

Alpha Smooth Muscle Actin ◽

Developmental Gene Expression ◽

Alveolar Development

The halogen bromine (Br2) is used extensively in industry and stored and transported in large quantities. Its accidental or malicious release into the atmosphere has resulted in significant casualties. The pathophysiology of Br2-induced lung injury has been studied in adult animals, but the consequences of Br2 exposure to the developing lung are completely unknown. We exposed neonatal mouse littermates on postnatal day 3 (P3) to either Br2 at 400 ppm for 30 min (400/30), to Br2 at 600 ppm for 30 min (600/30), or to room air, then returned them to their dams and observed until P14. Mice exposed to Br2 had decreased survival (S) and had decreased weight (W) at P14 in the 400/30 group (S = 63.5%, W = 6.67 ± 0.08) and in the 600/30 group (S = 36.1%, W = 5.13 ± 0.67) as compared with air breathing mice (S = 100%, W = 7.96 ± 0.30). Alveolar development was impaired, as evidenced by increased mean linear intercept at P14. At P14, Br2 exposed mice also exhibited a decrease of arterial partial pressure of oxygen, decreased quasi-static lung compliance, as well as increased alpha smooth muscle actin mRNA and protein and increased mRNA for IL-1β, IL-6, CXCL1, and TNFα. Global gene expression, evaluated by RNA sequencing and Ingenuity Pathway Analysis, revealed persistent abnormalities in gene expression profiles at P14 involving pathways of “formation of lung” and “pulmonary development.” The data indicate that Br2 inhalation injury early in life results in severe lung developmental consequences, wherein persistent inflammation and global altered developmental gene expression are likely mechanistic contributors.

Download Full-text