scholarly journals Extensive transgressive gene expression in a homoploid hybrid species

2021 ◽  
Author(s):  
Homa Papoli Yazdi ◽  
Melissah Rowe ◽  
Mark Ravinet ◽  
Glenn-Peter Sætre ◽  
Caroline Øien Guldvog ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
F1 Hybrids ◽  
Parent Species ◽  
Hybrid Species ◽  
Homoploid Hybrid ◽  
Open Question ◽  
Novel Variation

Hybridization is increasingly recognized as an important evolutionary force contributing novel variation for selection to act on. While mis-expression in F1 hybrids is well documented, how gene expression evolves in stabilized hybrid taxa and contributes novel variation remains an open question, especially for hybrid species without an increase in ploidy. As gene expression evolves in a stabilizing manner, break-up of co-evolved cis- and trans-regulatory elements could lead to transgressive patterns of gene expression in hybrids. Here, we address to what extent gonad gene expression has evolved in an old homoploid hybrid, Italian sparrow, Passer italiae. Through comparing the gene expression of parental species and F1 hybrids to that of the Italian sparrow, we find evidence for strongly transgressive expression in the Italian sparrow, with 22% of the testis genes exhibiting expression patterns outside the range of both parent species, compared to only 0.37% in the F1s. In contrast, Italian sparrow ovary expression was similar to that of one parent species, the house sparrow (P. domesticus). Moreover, the Italian sparrow testis transcriptome is 26.2 -26.6 times as diverged from those of the parent species compared to how divergent their transcriptomes are in spite of it being genetically intermediate. This highlights the potential for regulation of gene expression to produce novel variation following hybridization. Genes involved in energy production and protein synthesis are enriched in the subset that is over-dominantly expressed in Italian sparrow testis, suggesting that selection on key functions have molded the hybrid transcriptome.

A Global Vista of the Epigenomic State of the Mouse Submandibular Gland

2021 ◽  
pp. 002203452110120
Author(s):  
C. Gluck ◽  
S. Min ◽  
A. Oyelakin ◽  
M. Che ◽  
E. Horeth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Submandibular Salivary Gland ◽  
Data Sets ◽  
Control Mechanisms ◽  
Chromatin Immunoprecipitation Sequencing

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

scholarly journals Synthetic gene regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae

2019 ◽  
Author(s):  
Robin A. Sorg ◽  
Clement Gallay ◽  
Jan-Willem Veening
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Combinatorial Libraries ◽  
Regulatory Elements ◽  
Expression Control ◽  
Gene Expression Control

AbstractStreptococcus pneumoniae can cause disease in various human tissues and organs, including the ear, the brain, the blood and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control in S. pneumoniae. A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND and IMPLY gates. Finally, we demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity of S. pneumoniae.

scholarly journals Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

2020 ◽  
Author(s):  
Devanshi Patel ◽  
Xiaoling Zhang ◽  
John J. Farrell ◽  
Jaeyoon Chung ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

scholarly journals What functional genomics has taught us about transcriptional regulation in malaria parasites

2019 ◽  
Vol 18 (5) ◽  
pp. 290-301 ◽  
Author(s):  
Christa G Toenhake ◽  
Richárd Bártfai
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Life Cycle ◽  
Functional Genomics ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Complex Life Cycle ◽  
Malaria Parasites ◽  
Gene Regulatory

Abstract Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms. Recently, considerable progress has been made in identifying sequence-specific transcription factors and DNA-encoded regulatory elements. Here, we review the insights obtained from these efforts including the characterization of core promoters, the involvement of sequence-specific transcription factors in life cycle progression and the mapping of gene regulatory elements. Furthermore, we discuss recent developments in the field of functional genomics and how they might contribute to further characterization of this complex gene regulatory network.

scholarly journals Comparative Genomics and Transcriptomics To Analyze Fruiting Body Development in Filamentous Ascomycetes

Genetics ◽  
2019 ◽  
Vol 213 (4) ◽  
pp. 1545-1563 ◽  
Author(s):  
Ramona Lütkenhaus ◽  
Stefanie Traeger ◽  
Jan Breuer ◽  
Laia Carreté ◽  
Alan Kuo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fruiting Body ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Comparative Transcriptomics ◽  
Fruiting Bodies ◽  
Body Development ◽  
Fruiting Body Development ◽  
Genes Encoding

Many filamentous ascomycetes develop three-dimensional fruiting bodies for production and dispersal of sexual spores. Fruiting bodies are among the most complex structures differentiated by ascomycetes; however, the molecular mechanisms underlying this process are insufficiently understood. Previous comparative transcriptomics analyses of fruiting body development in different ascomycetes suggested that there might be a core set of genes that are transcriptionally regulated in a similar manner across species. Conserved patterns of gene expression can be indicative of functional relevance, and therefore such a set of genes might constitute promising candidates for functional analyses. In this study, we have sequenced the genome of the Pezizomycete Ascodesmis nigricans, and performed comparative transcriptomics of developing fruiting bodies of this fungus, the Pezizomycete Pyronema confluens, and the Sordariomycete Sordaria macrospora. With only 27 Mb, the A. nigricans genome is the smallest Pezizomycete genome sequenced to date. Comparative transcriptomics indicated that gene expression patterns in developing fruiting bodies of the three species are more similar to each other than to nonsexual hyphae of the same species. An analysis of 83 genes that are upregulated only during fruiting body development in all three species revealed 23 genes encoding proteins with predicted roles in vesicle transport, the endomembrane system, or transport across membranes, and 13 genes encoding proteins with predicted roles in chromatin organization or the regulation of gene expression. Among four genes chosen for functional analysis by deletion in S. macrospora, three were shown to be involved in fruiting body formation, including two predicted chromatin modifier genes.

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.

Identification of a Gain-of-Function SNP Causing a New Model of α-Thalassaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 523-523
Author(s):  
Marco De Gobbi ◽  
Vip Viprakasit ◽  
Pieter J. de Jong ◽  
Yuko Yoshinaga ◽  
Jan-Fang Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Globin Gene ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Regulatory Elements ◽  
Causative Mutation ◽  
Regulatory Sequences ◽  
Chromosome 16 ◽  
Upstream Regulatory Sequences

Abstract The human α globin cluster includes an embryonic gene ζ and 2 fetal/adult genes (α2 and α1) arranged along the chromosome in the order in which they are expressed in development (5′-ζ-pseudoζ- αD- α2-α1-𝛉-3′). Fully activated expression of these genes in erythroid cells depends on upstream regulatory elements of which HS-40, located 40kb upstream of the cluster, appears to exert the greatest effect. We have recently shown that during terminal differentiation, key transcription factors (GATA-2, GATA-1, NF-E2, SCL complex) sequentially bind the α promoters and their regulatory elements and a domain of histone acetylation develops which eventually encompasses the entire α globin cluster including the upstream regulatory sequences. α-thalassemia most frequently results from deletions or point mutations affecting the structural α globin genes, but may also result from rare sporadic deletions which remove the upstream regulatory sequences. In a single family α globin expression was silenced by a mutation which drives an anti-sense RNA through the α gene. Alpha thalassemia may also result from inherited and acquired mutations in a trans-acting factor called ATRX. Over the past few years we have continued to screen for new mechanisms which lead to α thalassemia and thereby elucidate new principles underlying the regulation of gene expression in hemopoiesis. Here we describe a new mechanism of α thalassemia occurring in Pacific Islanders in whom we could detect no mutations or rearrangements in the α globin gene locus. Despite this, extensive genetic analysis showed unequivocally that the causative mutation is linked to the terminal 169kb of chromosome 16 (Viprakasit et al accompanying abstract). Analysis of globin synthesis, steady state RNA levels and detection of RNA in situ demonstrated that the mutation downregulates α globin transcription. To identify the mutation, we constructed a new BAC library from an affected homozygote, isolated and re-sequenced the candidate region and focussed further analysis on 8 SNPS within the α globin cluster, one of which creates a new GATA-1 binding site (GACA>GATA). Using primary erythroblasts from normal individuals and patients with this form of thalassemia, together with interspecific hybrids containing either the normal or abnormal copy of chromosome 16, we have shown that this SNP creates a new binding site in vivo for GATA-1 and the SCL complex. Furthermore, the chromatin at this site becomes activated as judged by acetylation of histone H3 and H4 (H3ac2 and H4ac4) and methylation of histone H3 (H3K4me2). Based on these data we postulate that an active transcriptional complex binding this new GATA site created by the SNP-mutation, could distract the upstream regulatory regions, which normally interact with the α globin promoter, and silence α globin gene expression. This model thus represents a new example of α globin gene down-regulation and a new mechanism by which gene expression can be perturbed during hemopoiesis.

scholarly journals Hepatic gene expression patterns in thyroid hormone-treated hypothyroid rats

2003 ◽  
Vol 31 (2) ◽  
pp. 291-303 ◽  
Author(s):  
JM Weitzel ◽  
S Hamann ◽  
M Jauk ◽  
M Lacey ◽  
A Filbry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Activation Mechanism ◽  
Gene Expression Patterns ◽  
Peroxisome Proliferator ◽  
Gene Promoters ◽  
Protein Levels

Thyroid hormone (T3) is essential for normal development, differentiation and metabolic balance. We have performed DNA microarray experiments using hepatic RNA from hypothyroid and T3-treated hypothyroid rats in order to characterize T3-induced gene expression patterns after various time points (6, 24 and 48 h after the administration of the hormone). Sixty-two of 4608 different genes displayed a reproducible T3-response, and cluster analysis divided these differentially regulated genes into six expression patterns. Thirty-six genes were not significantly regulated within the first 24 h. Transient transfection experiments of eight late-induced gene promoters failed to detect a thyroid hormone response element within their regulatory elements, suggesting an indirect activation mechanism(s). In search for an intermediate factor of T3 action, we examined whether various rather ubiquitous transcription factors, peroxisome proliferator-activated receptors (PPARs) and coactivators of the PPARgamma coactivator 1 family (PGC-1) are regulated by T3. Only PPARgamma and PERC/PGC-1beta exhibit a significant T3-response within the first 6 h after treatment, identifying these factors as candidate components for mediating the late-induced expression pattern. Regulation of early-induced genes within the first 6 h after administration of T3 on transcript levels correlates with altered protein levels after 24 and 48 h in vivo.

scholarly journals Regulation of Gene Expression Patterns in Mosquito Reproduction

PLoS Genetics ◽  
2015 ◽  
Vol 11 (8) ◽  
pp. e1005450 ◽  
Author(s):  
Sourav Roy ◽  
Tusar T. Saha ◽  
Lisa Johnson ◽  
Bo Zhao ◽  
Jisu Ha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Gene Expression Patterns
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