scholarly journals mtDNA eQTLs and the m1A 16S rRNA modification explain mtDNA tissue-specific gene expression pattern in humans

2018 ◽  
Author(s):  
Tal Cohen ◽  
Chen Mordechai ◽  
Alal Eran ◽  
Dan Mishmar
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
16S Rrna ◽  
Gene Expression Pattern ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Dependent Manner ◽  
Rna Seq ◽  
Genome Wide ◽  
The Impact

Expression quantitative trait loci (eQTLs) are instrumental in genome-wide identification of regulatory elements, yet were overlooked in the mitochondrial DNA (mtDNA). By analyzing 5079 RNA-seq samples from 23 tissues we identified association of ancient mtDNA SNPs (haplogroups T2, L2, J2 and V) and recurrent SNPs (mtDNA positions 263, 750, 1438 and 10398) with tissue-dependent mtDNA gene-expression. Since the recurrent SNPs independently occurred in different mtDNA genetic backgrounds, they constitute the best candidates to be causal eQTLs. Secondly, the discovery of mtDNA eQTLs in both coding and non-coding mtDNA regions, propose the identification of novel mtDNA regulatory elements. Third, we identified association between low m1A 947 MT-RNR2 (16S) rRNA modification levels and altered mtDNA gene-expression in twelve tissues. Such association disappeared in skin which was exposed to sun, as compared to sun-unexposed skin from the same individuals, thus supporting the impact of UV on mtDNA gene expression. Taken together, our findings reveal that both mtDNA SNPs and mt-rRNA modification affect mtDNA gene expression in a tissue-dependent manner.

scholarly journals Identification and classification of cis-regulatory elements in the amphipod crustacean Parhyale hawaiensis

2021 ◽  
Author(s):  
Dennis A Sun ◽  
Nipam H Patel
Keyword(s):  
Gene Expression ◽  
Genome Annotation ◽  
Time Course ◽  
Regulatory Elements ◽  
Rna Seq ◽  
Genome Wide ◽  
Long Read ◽  
Amphipod Crustacean ◽  
Accessible Chromatin

AbstractEmerging research organisms enable the study of biology that cannot be addressed using classical “model” organisms. The development of novel data resources can accelerate research in such animals. Here, we present new functional genomic resources for the amphipod crustacean Parhyale hawaiensis, facilitating the exploration of gene regulatory evolution using this emerging research organism. We use Omni-ATAC-Seq, an improved form of the Assay for Transposase-Accessible Chromatin coupled with next-generation sequencing (ATAC-Seq), to identify accessible chromatin genome-wide across a broad time course of Parhyale embryonic development. This time course encompasses many major morphological events, including segmentation, body regionalization, gut morphogenesis, and limb development. In addition, we use short- and long-read RNA-Seq to generate an improved Parhyale genome annotation, enabling deeper classification of identified regulatory elements. We leverage a variety of bioinformatic tools to discover differential accessibility, predict nucleosome positioning, infer transcription factor binding, cluster peaks based on accessibility dynamics, classify biological functions, and correlate gene expression with accessibility. Using a Minos transposase reporter system, we demonstrate the potential to identify novel regulatory elements using this approach, including distal regulatory elements. This work provides a platform for the identification of novel developmental regulatory elements in Parhyale, and offers a framework for performing such experiments in other emerging research organisms.Primary Findings-Omni-ATAC-Seq identifies cis-regulatory elements genome-wide during crustacean embryogenesis-Combined short- and long-read RNA-Seq improves the Parhyale genome annotation-ImpulseDE2 analysis identifies dynamically regulated candidate regulatory elements-NucleoATAC and HINT-ATAC enable inference of nucleosome occupancy and transcription factor binding-Fuzzy clustering reveals peaks with distinct accessibility and chromatin dynamics-Integration of accessibility and gene expression reveals possible enhancers and repressors-Omni-ATAC can identify known and novel regulatory elements

scholarly journals Differential evolution in 3′UTRs leads to specific gene expression in Staphylococcus

2020 ◽  
Vol 48 (5) ◽  
pp. 2544-2563 ◽  
Author(s):  
Pilar Menendez-Gil ◽  
Carlos J Caballero ◽  
Arancha Catalan-Moreno ◽  
Naiara Irurzun ◽  
Inigo Barrio-Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Bacterial Species ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Species Differentiation ◽  
Orthologous Genes ◽  
Genome Wide ◽  
Sequence Variations ◽  
Species Specific

Abstract The evolution of gene expression regulation has contributed to species differentiation. The 3′ untranslated regions (3′UTRs) of mRNAs include regulatory elements that modulate gene expression; however, our knowledge of their implications in the divergence of bacterial species is currently limited. In this study, we performed genome-wide comparative analyses of mRNAs encoding orthologous proteins from the genus Staphylococcus and found that mRNA conservation was lost mostly downstream of the coding sequence (CDS), indicating the presence of high sequence diversity in the 3′UTRs of orthologous genes. Transcriptomic mapping of different staphylococcal species confirmed that 3′UTRs were also variable in length. We constructed chimeric mRNAs carrying the 3′UTR of orthologous genes and demonstrated that 3′UTR sequence variations affect protein production. This suggested that species-specific functional 3′UTRs might be specifically selected during evolution. 3′UTR variations may occur through different processes, including gene rearrangements, local nucleotide changes, and the transposition of insertion sequences. By extending the conservation analyses to specific 3′UTRs, as well as the entire set of Escherichia coli and Bacillus subtilis mRNAs, we showed that 3′UTR variability is widespread in bacteria. In summary, our work unveils an evolutionary bias within 3′UTRs that results in species-specific non-coding sequences that may contribute to bacterial diversity.

scholarly journals Beyond the ENCODE project: using genomics and epigenomics strategies to study enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130022 ◽  
Author(s):  
Noboru Jo Sakabe ◽  
Marcelo A. Nobrega
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Dna Interaction ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Genome Wide ◽  
Identify Transcription Factor ◽  
Specific Proteins ◽  
Species Specific

The complex expression patterns observed for many genes are often regulated by distal transcription enhancers. Changes in the nucleotide sequences of enhancers may therefore lead to changes in gene expression, representing a central mechanism by which organisms evolve. With the development of the experimental technique of chromatin immunoprecipitation (ChIP), in which discrete regions of the genome bound by specific proteins can be identified, it is now possible to identify transcription factor binding events (putative cis -regulatory elements) in entire genomes. Comparing protein–DNA binding maps allows us, for the first time, to attempt to identify regulatory differences and infer global patterns of change in gene expression across species. Here, we review studies that used genome-wide ChIP to study the evolution of enhancers. The trend is one of high divergence of cis -regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. We speculate on the meaning of the differences observed and discuss that although ChIP experiments identify the biochemical event of protein–DNA interaction, it cannot determine whether the event results in a biological function, and therefore more studies are required to establish the effect of divergence of binding events on species-specific gene expression.

scholarly journals Interferon-regulated genetic programs and JAK/STAT pathway activate the intronic promoter of the short ACE2 isoform in renal proximal tubules

2021 ◽  
Author(s):  
Jakub Jankowski ◽  
Hye Kyung Lee ◽  
Julia Wilflingseder ◽  
Lothar Hennighausen
Keyword(s):  
Gene Expression ◽  
Proximal Tubule ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Rna Seq ◽  
Angiotensin Converting Enzyme 2 ◽  
Genome Wide ◽  
Cytokine Stimulation

SummaryRecently, a short, interferon-inducible isoform of Angiotensin-Converting Enzyme 2 (ACE2), dACE2 was identified. ACE2 is a SARS-Cov-2 receptor and changes in its renal expression have been linked to several human nephropathies. These changes were never analyzed in context of dACE2, as its expression was not investigated in the kidney. We used Human Primary Proximal Tubule (HPPT) cells to show genome-wide gene expression patterns after cytokine stimulation, with emphasis on the ACE2/dACE2 locus. Putative regulatory elements controlling dACE2 expression were identified using ChIP-seq and RNA-seq. qRT-PCR differentiating between ACE2 and dACE2 revealed 300- and 600-fold upregulation of dACE2 by IFNα and IFNβ, respectively, while full length ACE2 expression was almost unchanged. JAK inhibitor ruxolitinib ablated STAT1 and dACE2 expression after interferon treatment. Finally, with RNA-seq, we identified a set of genes, largely immune-related, induced by cytokine treatment. These gene expression profiles provide new insights into cytokine response of proximal tubule cells.

scholarly journals Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver

2018 ◽  
Author(s):  
Minal Çalışkan ◽  
Elisabetta Manduchi ◽  
H. Shanker Rao ◽  
Julian A Segert ◽  
Marcia Holsbach Beltrame ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Histone Modification ◽  
Human Liver ◽  
Complex Disease ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Chromatin Interaction ◽  
Genome Wide ◽  
The Impact

ABSTRACTDeciphering the impact of genetic variation on gene regulation is fundamental to understanding common, complex human diseases. Although histone modifications are important markers of gene regulatory regions of the genome, any specific histone modification has not been assayed in more than a few individuals in the human liver. As a result, the impacts of genetic variation that direct histone modification states in the liver are poorly understood. Here, we generate the most comprehensive genome-wide dataset of two epigenetic marks, H3K4me3 and H3K27ac, and annotate thousands of putative regulatory elements in the human liver. We integrate these findings with genome-wide gene expression data collected from the same human liver tissues and high-resolution promoter-focused chromatin interaction maps collected from human liver-derived HepG2 cells. We demonstrate widespread functional consequences of natural genetic variation on putative regulatory element activity and gene expression levels. Leveraging these extensive datasets, we fine-map a total of 77 GWAS loci that have been associated with at least one complex phenotype. Our results contribute to the repertoire of genes and regulatory mechanisms governing complex disease development and further the basic understanding of genetic and epigenetic regulation of gene expression in the human liver tissue.

scholarly journals Read trimming is not required for mapping and quantification of RNA-seq reads

2019 ◽  
Author(s):  
Yang Liao ◽  
Wei Shi
Keyword(s):  
Gene Expression ◽  
Rna Seq ◽  
Read Mapping ◽  
Genome Wide ◽  
Sequencing Quality ◽  
Total Data ◽  
Order Of Magnitude ◽  
Gene Expression Quantification ◽  
The Impact ◽  
Genome Wide Gene Expression

AbstractRNA sequencing (RNA-seq) is currently the standard method for genome-wide gene expression profiling. RNA-seq reads often need to be mapped to a reference genome before read counts can be produced for genes. Read trimming methods have been developed to assist read mapping by removing adapter sequences and low-sequencing-quality bases. It is however unclear what is the impact of read trimming on the quantification of RNA-seq gene expression, an important task in the analysis of RNA-seq data. In this study, we used a benchmark RNA-seq dataset generated in the SEQC project to assess the impact of read trimming on mapping and quantification of RNA-seq reads. We found that adapter sequences can be effectively removed by the read aligner via its ‘soft-clipping’ procedure and many low-sequencing-quality bases, which would be removed by read trimming tools, were rescued by the aligner. Accuracy of gene expression quantification from using untrimmed reads was found to be comparable to or slightly better than that from using trimmed reads, based on expression of >900 genes measured by real-time PCR. Total data analysis time was reduced by up to an order of magnitude when read trimming was not performed. Our study suggests that read trimming is a redundant process in the quantification of RNA-seq expression data.

scholarly journals Transcriptome analysis of Plasmodium berghei during exo-erythrocytic development

2019 ◽  
Author(s):  
Reto Caldelari ◽  
Sunil Dogga ◽  
Marc W. Schmid ◽  
Blandine Franke-Fayard ◽  
Chris J Janse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Plasmodium Berghei ◽  
Expression Profiles ◽  
Specific Gene ◽  
Rna Seq ◽  
Erythrocytic Stage ◽  
Liver Stage ◽  
Specific Gene Expression ◽  
Genome Wide

SummaryThe complex life cycle of malaria parasites requires well-orchestrated stage specific gene expression. In the vertebrate host the parasites grow and multiply by schizogony in two different environments: within erythrocytes and within hepatocytes. Whereas erythrocytic parasites are rather well-studied in this respect, relatively little is known about the exo-erythrocytic stages. In an attempt to fill this gap, we performed genome wide RNA-seq analyses of various exo-erythrocytic stages of Plasmodium berghei including sporozoites, samples from a time-course of liver stage development and detached cells, which contain infectious merozoites and represent the final step in exo-erythrocytic development. The analysis represents the completion of the transcriptome of the entire life cycle of P. berghei parasites with temporal detailed analysis of the liver stage allowing segmentation of the transcriptome across the progression of the life cycle. We have used these RNA-seq data from different developmental stages to cluster genes with similar expression profiles, in order to infer their functions. A comparison with published data of other parasite stages confirmed stage-specific gene expression and revealed numerous genes that are expressed differentially in blood and exo-erythrocytic stages. One of the most exo-erythrocytic stage-specific genes was PBANKA_1003900, which has previously been annotated as a “gametocyte specific protein”. The promoter of this gene drove high GFP expression in exo-erythrocytic stages, confirming its expression profile seen by RNA-seq. The comparative analysis of the genome wide mRNA expression profiles of erythrocytic and different exo-erythrocytic stages improves our understanding of gene regulation of Plasmodium parasites and can be used to model exo-erythrocytic stage metabolic networks and identify differences in metabolic processes during schizogony in erythrocytes and hepatocytes.

scholarly journals Transcriptome analysis of Plasmodium berghei during exo-erythrocytic development

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Reto Caldelari ◽  
Sunil Dogga ◽  
Marc W. Schmid ◽  
Blandine Franke-Fayard ◽  
Chris J. Janse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Plasmodium Berghei ◽  
Expression Profiles ◽  
Specific Gene ◽  
Rna Seq ◽  
Erythrocytic Stage ◽  
Liver Stage ◽  
Specific Gene Expression ◽  
Genome Wide

Abstract Background The complex life cycle of malaria parasites requires well-orchestrated stage specific gene expression. In the vertebrate host the parasites grow and multiply by schizogony in two different environments: within erythrocytes and within hepatocytes. Whereas erythrocytic parasites are well-studied in this respect, relatively little is known about the exo-erythrocytic stages. Methods In an attempt to fill this gap, genome wide RNA-seq analyses of various exo-erythrocytic stages of Plasmodium berghei including sporozoites, samples from a time-course of liver stage development and detached cells were performed. These latter contain infectious merozoites and represent the final step in exo-erythrocytic development. Results The analysis represents the complete transcriptome of the entire life cycle of P. berghei parasites with temporal detailed analysis of the liver stage allowing comparison of gene expression across the progression of the life cycle. These RNA-seq data from different developmental stages were used to cluster genes with similar expression profiles, in order to infer their functions. A comparison with published data from other parasite stages confirmed stage-specific gene expression and revealed numerous genes that are expressed differentially in blood and exo-erythrocytic stages. One of the most exo-erythrocytic stage-specific genes was PBANKA_1003900, which has previously been annotated as a “gametocyte specific protein”. The promoter of this gene drove high GFP expression in exo-erythrocytic stages, confirming its expression profile seen by RNA-seq. Conclusions The comparative analysis of the genome wide mRNA expression profiles of erythrocytic and different exo-erythrocytic stages could be used to improve the understanding of gene regulation in Plasmodium parasites and can be used to model exo-erythrocytic stage metabolic networks toward the identification of differences in metabolic processes during schizogony in erythrocytes and hepatocytes.

scholarly journals Repression precedes the stepwise evolution of a highly specific gene expression pattern

2020 ◽  
Author(s):  
Jian Pu ◽  
Zinan Wang ◽  
Haosu Cong ◽  
Jacqueline S.R. Chin ◽  
Jessa Justen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Regulatory Elements ◽  
Fatty Acyl ◽  
Specific Gene ◽  
Spatial Expression ◽  
Origin And Evolution ◽  
And Function

AbstractWell-controlled gene expression is critical for the proper development and function of many traits. Highly-specific temporal and spatial expression patterns are often due to the overlapping activities of activator and repressor sequences that form cis-regulatory elements called enhancers. While many studies have shown that evolutionary changes in enhancers can result in novel traits, few studies illuminate how enhancers originate, how activator and repressor sequences interact during enhancer evolution, and the order in which they evolve. Here, we traced the evolutionary origin of a recently evolved enhancer that drives the expression of the fatty acyl-CoA elongase, bond, specifically in the semicircular wall epithelium (swe) of the Drosophila male ejaculatory bulb (EB). We show that this enhancer consists of two activator regions that drive bond expression in the entire EB and a repressor region that restricts expression specifically to the EB swe. Interestingly, the repressor region preceded the evolution of the two activator regions. The evolution of the first activator region, consisting of two putative Abdominal-B sites, did not drive expression in the EB due to the action of the repressor region. Expression of bond in the EB swe requires the evolution of the second activator region, which does not drive expression on its own, but synergizes with the first activator region and the repressor region to produce a highly-specific spatial expression pattern. Our results show that the origin and evolution of a novel enhancer require multiple steps and the evolution of repressor sequences can precede the evolution of activator sequences.

Acetylation-Dependent Interaction of GATA-1 with the Potential Mitotic “Bookmarking” Protein Brd3.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2598-2598
Author(s):  
Janine M Lamonica ◽  
Stephan Kadauke ◽  
Wulan Deng ◽  
Gerd Blobel
Keyword(s):  
Gene Expression ◽  
Conflicts Of Interest ◽  
Memory Function ◽  
Great Majority ◽  
Underlying Mechanism ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Dependent Manner

Abstract Abstract 2598 Acetylation of the transcription factor GATA-1 facilitates its ability to drive erythroid differentiation by enhancing its association with in vivo target sites. However, the underlying mechanism through which GATA-1 acetylation functions has remained elusive. To test whether GATA-1 acetylation serves to recruit essential cofactors, we performed a peptide affinity screen and identified Brd3 as an acetylated GATA-1 interacting partner. Brd3 belongs to the BET protein family that also includes Brd2, Brd4, and Brdt, and is characterized by tandem bromodomains (BD1 and BD2) and an extraterminal (ET) domain. We show that Brd3 and GATA-1 physically interact in an acetylation-dependent manner in vitro and in vivo. Mapping studies revealed that the interaction depends on BD1 of Brd3 and one of the two major acetylation sites that resides near the C terminal zinc finger of GATA-1. By ChIP-seq and ChIP-qPCR, endogenous Brd3 is recruited to virtually all GATA-1-occupied regulatory elements in erythroid cells, including both GATA-1activated and repressed genes. Although Brd3 has been reported to associate with acetylated histones along the entire length of transcribed genes, we found that Brd3 recruitment correlates poorly with histone acetylation along gene bodies. In agreement with our biochemical data, an intact BD1 is essential for the in vivo recruitment of Brd3 to GATA-1-occupied elements, further demonstrating that acetylation of GATA-1 is essential for Brd3 association in vivo. Notably, a pharmacological compound that targets acetyl lysine binding sites in BD1 and BD2 disrupts the Brd3/GATA-1 interaction in vitro, diminishes Brd3 and GATA-1 association at key erythroid genes in vivo, and impairs GATA-1 target gene expression and erythroid maturation. In concert, these findings suggest a mechanism by which the first bromodomain of Brd3 recognizes acetyl-lysines on GATA-1 to facilitate GATA-1 chromatin occupancy. These studies raise an interesting question: In contrast to the great majority of transcription factors, BET family proteins bind to chromatin during mitosis and might serve an epigenetic memory function to properly reactivate gene transcription upon exit of mitosis. We are currently investigating whether Brd3 functions by bookmarking GATA-1-bound sites throughout mitosis to aid in transcriptional memory and stability of lineage specific gene expression. Disclosures: No relevant conflicts of interest to declare.

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