scholarly journals Transcriptional regulation of a myeloid-lineage specific gene lysozyme C during zebrafish myelopoiesis

2009 ◽  
Vol 126 (5-6) ◽  
pp. 314-323 ◽  
Author(s):  
Tetsuya Kitaguchi ◽  
Koichi Kawakami ◽  
Atsuo Kawahara
Keyword(s):  
Transcriptional Regulation ◽  
Specific Gene ◽  
Myeloid Lineage ◽  
Lineage Specific Gene ◽  
Lysozyme C

scholarly journals The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
José L Ruiz ◽  
Lisa C Ranford-Cartwright ◽  
Elena Gómez-Díaz
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Anopheles Gambiae ◽  
Mosquito Control ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Malaria Vectors ◽  
Specific Gene ◽  
Mosquito Vector ◽  
Human Malaria

Abstract Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by the assay for transposase-accessible chromatin by sequencing (ATAC-seq) in laboratory-reared A. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data, we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue-specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that were annotated to mosquito immune-related genes. Not only is this study important for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information we produced also has great potential for developing new mosquito-control and anti-malaria strategies.

A Variant Noncoding Region Regulates Prrx1 and Predisposes to Atrial Arrhythmias

2021 ◽  
Author(s):  
Fernanda M Bosada ◽  
Mathilde R Rivaud ◽  
Jae-Sun Uhm ◽  
Sander Verheule ◽  
Karel van Duijvenboden ◽  
...  
Keyword(s):  
Sodium Current ◽  
Association Studies ◽  
Noncoding Region ◽  
Specific Gene ◽  
Genome Wide Association Studies ◽  
Enhancer Activity ◽  
Atrial Cardiomyocytes ◽  
The Impact ◽  
Lineage Specific Gene

Rationale: Atrial Fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice. Genome-wide association studies have identified AF-associated common variants across 100+ genomic loci, but the mechanism underlying the impact of these variant loci on AF susceptibility in vivo has remained largely undefined. One such variant region, highly associated with AF, is found at 1q24, close to PRRX1, encoding the Paired Related Homeobox 1 transcription factor. Objective: To identify the mechanistic link between the variant region at 1q24 and AF predisposition. Methods and Results: The mouse orthologue of the noncoding variant genomic region (R1A) at 1q24 was deleted using CRISPR genome editing. Among the genes sharing the topologically associated domain with the deleted R1A region (Kifap3, Prrx1, Fmo2, Prrc2c), only the broadly expressed gene Prrx1 was downregulated in mutants, and only in cardiomyocytes. Expression and epigenetic profiling revealed that a cardiomyocyte lineage-specific gene program (Mhrt, Myh6, Rbm20, Tnnt2, Ttn, Ckm) was upregulated in R1A-/- atrial cardiomyocytes, and that Mef2 binding motifs were significantly enriched at differentially accessible chromatin sites. Consistently, Prrx1 suppressed Mef2-activated enhancer activity in HL-1 cells. Mice heterozygous or homozygous for the R1A deletion were susceptible to atrial arrhythmia induction, had atrial conduction slowing and more irregular RR intervals. Isolated R1A-/- mouse left atrial cardiomyocytes showed lower action potential upstroke velocities and sodium current, as well as increased systolic and diastolic calcium concentrations compared to controls. Conclusions: The noncoding AF variant region at 1q24 modulates Prrx1 expression in cardiomyocytes. Cardiomyocyte-specific reduction of Prrx1 expression upon deletion of the noncoding region leads to a profound induction of a cardiac lineage-specific gene program and to propensity for AF. These data indicate that AF-associated variants in humans may exert AF predisposition through reduced PRRX1 expression in cardiomyocytes.

scholarly journals Network-based microsynteny analysis identifies major differences and genomic outliers in mammalian and angiosperm genomes

2019 ◽  
Vol 116 (6) ◽  
pp. 2165-2174 ◽  
Author(s):  
Tao Zhao ◽  
M. Eric Schranz
Keyword(s):  
Gene Families ◽  
Single Copy ◽  
Specific Gene ◽  
Phylogenetic Groups ◽  
History Of ◽  
Mammalian Genomes ◽  
Syntenic Conservation ◽  
Genome Assemblies ◽  
Lineage Specific Gene ◽  
Relative Gene

A comprehensive analysis of relative gene order, or microsynteny, can provide valuable information for understanding the evolutionary history of genes and genomes, and ultimately traits and species, across broad phylogenetic groups and divergence times. We have used our network-based phylogenomic synteny analysis pipeline to first analyze the overall patterns and major differences between 87 mammalian and 107 angiosperm genomes. These two important groups have both evolved and radiated over the last ∼170 MYR. Secondly, we identified the genomic outliers or “rebel genes” within each clade. We theorize that rebel genes potentially have influenced trait and lineage evolution. Microsynteny networks use genes as nodes and syntenic relationships between genes as edges. Networks were decomposed into clusters using the Infomap algorithm, followed by phylogenomic copy-number profiling of each cluster. The differences in syntenic properties of all annotated gene families, including BUSCO genes, between the two clades are striking: most genes are single copy and syntenic across mammalian genomes, whereas most genes are multicopy and/or have lineage-specific distributions for angiosperms. We propose microsynteny scores as an alternative and complementary metric to BUSCO for assessing genome assemblies. We further found that the rebel genes are different between the two groups: lineage-specific gene transpositions are unusual in mammals, whereas single-copy highly syntenic genes are rare for flowering plants. We illustrate several examples of mammalian transpositions, such as brain-development genes in primates, and syntenic conservation across angiosperms, such as single-copy genes related to photosynthesis. Future experimental work can test if these are indeed rebels with a cause.

scholarly journals Dynamic changes in cis-regulatory occupancy by Six1 and its cooperative interactions with distinct cofactors drive lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium

2020 ◽  
Vol 48 (6) ◽  
pp. 2880-2896 ◽  
Author(s):  
Jun Li ◽  
Ting Zhang ◽  
Aarthi Ramakrishnan ◽  
Bernd Fritzsch ◽  
Jinshu Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Sensory Epithelium ◽  
Hair Bundle ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Wide Range ◽  
Cell Type Specific ◽  
Lineage Specific Gene

Abstract The transcription factor Six1 is essential for induction of sensory cell fate and formation of auditory sensory epithelium, but how it activates gene expression programs to generate distinct cell-types remains unknown. Here, we perform genome-wide characterization of Six1 binding at different stages of auditory sensory epithelium development and find that Six1-binding to cis-regulatory elements changes dramatically at cell-state transitions. Intriguingly, Six1 pre-occupies enhancers of cell-type-specific regulators and effectors before their expression. We demonstrate in-vivo cell-type-specific activity of Six1-bound novel enhancers of Pbx1, Fgf8, Dusp6, Vangl2, the hair-cell master regulator Atoh1 and a cascade of Atoh1’s downstream factors, including Pou4f3 and Gfi1. A subset of Six1-bound sites carry consensus-sequences for its downstream factors, including Atoh1, Gfi1, Pou4f3, Gata3 and Pbx1, all of which physically interact with Six1. Motif analysis identifies RFX/X-box as one of the most significantly enriched motifs in Six1-bound sites, and we demonstrate that Six1-RFX proteins cooperatively regulate gene expression through binding to SIX:RFX-motifs. Six1 targets a wide range of hair-bundle regulators and late Six1 deletion disrupts hair-bundle polarity. This study provides a mechanistic understanding of how Six1 cooperates with distinct cofactors in feedforward loops to control lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium.

scholarly journals Papain-like cysteine proteases in Carica papaya: lineage-specific gene duplication and expansion

BMC Genomics ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Juan Liu ◽  
Anupma Sharma ◽  
Marie Jamille Niewiara ◽  
Ratnesh Singh ◽  
Ray Ming ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Carica Papaya ◽  
Cysteine Proteases ◽  
Specific Gene ◽  
Lineage Specific Gene

scholarly journals Core regulatory circuitries in defining cancer cell identity across the malignant spectrum

Open Biology ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 200121
Author(s):  
Leila Jahangiri ◽  
Loukia Tsaprouni ◽  
Ricky M. Trigg ◽  
John A. Williams ◽  
Georgios V. Gkoutos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Chromatin Structure ◽  
Drug Targets ◽  
Genetic Alterations ◽  
Specific Gene ◽  
Molecular Dissection ◽  
Cell Identity ◽  
Lineage Specific Gene

Gene expression programmes driving cell identity are established by tightly regulated transcription factors that auto- and cross-regulate in a feed-forward manner, forming core regulatory circuitries (CRCs). CRC transcription factors create and engage super-enhancers by recruiting acetylation writers depositing permissive H3K27ac chromatin marks. These super-enhancers are largely associated with BET proteins, including BRD4, that influence higher-order chromatin structure. The orchestration of these events triggers accessibility of RNA polymerase machinery and the imposition of lineage-specific gene expression. In cancers, CRCs drive cell identity by superimposing developmental programmes on a background of genetic alterations. Further, the establishment and maintenance of oncogenic states are reliant on CRCs that drive factors involved in tumour development. Hence, the molecular dissection of CRC components driving cell identity and cancer state can contribute to elucidating mechanisms of diversion from pre-determined developmental programmes and highlight cancer dependencies. These insights can provide valuable opportunities for identifying and re-purposing drug targets. In this article, we review the current understanding of CRCs across solid and liquid malignancies and avenues of investigation for drug development efforts. We also review techniques used to understand CRCs and elaborate the indication of discussed CRC transcription factors in the wider context of cancer CRC models.

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