scholarly journals An atlas of transcription factors expressed in the Drosophila melanogaster pupal terminalia

2019 ◽  
Author(s):  
Ben J. Vincent ◽  
Gavin R. Rice ◽  
Gabriella M. Wong ◽  
William J. Glassford ◽  
Kayla I. Downs ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Rna Seq ◽  
Pupal Development ◽  
Searchable Database ◽  
Gene Regulatory ◽  
Development And Evolution

AbstractDuring development, transcription factors and signaling molecules govern gene regulatory networks to direct the formation of unique morphologies. As changes in gene regulatory networks are often implicated in morphological evolution, mapping transcription factor landscapes is important, especially in tissues that undergo rapid evolutionary change. The terminalia (genital and anal structures) of Drosophila melanogaster and its close relatives exhibit dramatic changes in morphology between species. While previous studies have found network components important for patterning the larval genital disc, the networks governing adult structures during pupal development have remained uncharted. Here, we performed RNA-seq in whole Drosophila melanogaster terminalia followed by in situ hybridization for 100 highly expressed transcription factors during pupal development. We find that the terminalia is highly patterned during pupal stages and that specific transcription factors mark separate structures and substructures. Our results are housed online in a searchable database (flyterminalia.pitt.edu) where they can serve as a resource for the community. This work lays a foundation for future investigations into the gene regulatory networks governing the development and evolution of Drosophila terminalia.SummaryWe performed RNA-seq in whole Drosophila melanogaster terminalia (genitalia and analia) followed by in situ hybridization for 100 highly expressed transcription factors during pupal development. We find that the pupal terminalia is highly patterned with specific transcription factors marking separate structures and substructures. Our results are housed online in a searchable database (flyterminalia.pitt.edu) where they can serve as a resource for the community. This work lays a foundation for future investigations into the gene regulatory networks governing the development and evolution of Drosophila terminalia.

scholarly journals Inferring gene regulatory networks from single-cell RNA-seq temporal snapshot data requires higher-order moments

Patterns ◽  
2021 ◽  
Vol 2 (9) ◽  
pp. 100332
Author(s):  
N. Alexia Raharinirina ◽  
Felix Peppert ◽  
Max von Kleist ◽  
Christof Schütte ◽  
Vikram Sunkara
Keyword(s):  
Single Cell ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Higher Order ◽  
Rna Seq ◽  
Higher Order Moments ◽  
Gene Regulatory

scholarly journals Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shoujun Gu ◽  
Rafal Olszewski ◽  
Ian Taukulis ◽  
Zheng Wei ◽  
Daniel Martin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Adult Mouse ◽  
Stria Vascularis ◽  
Cell Types ◽  
Rna Seq ◽  
Root Cells ◽  
Transcriptional Profiles ◽  
Gene Regulatory

Abstract The stria vascularis (SV) in the cochlea generates and maintains the endocochlear potential, thereby playing a pivotal role in normal hearing. Knowing transcriptional profiles and gene regulatory networks of SV cell types establishes a basis for studying the mechanism underlying SV-related hearing loss. While we have previously characterized the expression profiles of major SV cell types in the adult mouse, transcriptional profiles of rare SV cell types remained elusive due to the limitation of cell capture in single-cell RNA-Seq. The role of these rare cell types in the homeostatic function of the adult SV remain largely undefined. In this study, we performed single-nucleus RNA-Seq on the adult mouse SV in conjunction with sample preservation treatments during the isolation steps. We distinguish rare SV cell types, including spindle cells and root cells, from other cell types, and characterize their transcriptional profiles. Furthermore, we also identify and validate novel specific markers for these rare SV cell types. Finally, we identify homeostatic gene regulatory networks within spindle and root cells, establishing a basis for understanding the functional roles of these cells in hearing. These novel findings will provide new insights for future work in SV-related hearing loss and hearing fluctuation.

scholarly journals Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets

2016 ◽  
Vol 113 (13) ◽  
pp. E1835-E1843 ◽  
Author(s):  
Mina Fazlollahi ◽  
Ivor Muroff ◽  
Eunjee Lee ◽  
Helen C. Causton ◽  
Harmen J. Bussemaker
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Nonsynonymous Mutation ◽  
Gene Regulatory ◽  
Genetic Modulators

Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae. We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.

scholarly journals Upregulation and cell specificity of C4 genes are derived from ancestral C3 gene regulatory networks

2020 ◽  
Author(s):  
Pallavi Singh ◽  
Sean R. Stevenson ◽  
Ivan Reyna-Llorens ◽  
Gregory Reeves ◽  
Tina B. Schreier ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Transcript Accumulation ◽  
Specific Expression ◽  
Cell Specificity ◽  
Distinct Cell ◽  
Gene Regulatory

ABSTRACTThe efficient C4 pathway is based on strong up-regulation of genes found in C3 plants, but also compartmentation of their expression into distinct cell-types such as the mesophyll and bundle sheath. Transcription factors associated with these phenomena have not been identified. To address this, we undertook genome-wide analysis of transcript accumulation, chromatin accessibility and transcription factor binding in C4Gynandropsis gynandra. From these data, two models relating to the molecular evolution of C4 photosynthesis are proposed. First, increased expression of C4 genes is associated with increased binding by MYB-related transcription factors. Second, mesophyll specific expression is associated with binding of homeodomain transcription factors. Overall, we conclude that during evolution of the complex C4 trait, C4 cycle genes gain cis-elements that operate in the C3 leaf such that they become integrated into existing gene regulatory networks associated with cell specificity and photosynthesis.

scholarly journals Revealing the Key Regulators of Cell Identity in the Human Adult Pancreas

2020 ◽  
Author(s):  
Lotte Vanheer ◽  
Andrea Alex Schiavo ◽  
Matthias Van Haele ◽  
Tine Haesen ◽  
Adrian Janiszewski ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
List Type ◽  
Cell Identity ◽  
Pancreatic Cell ◽  
Human Adult ◽  
Gene Regulatory ◽  
Cellular Identity

SUMMARYCellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA sequencing datasets of the human adult pancreas, totaling 7393 cells, and comprehensively reconstruct gene regulatory networks. We show that a network of 142 transcription factors forms distinct regulatory modules that characterize pancreatic cell types. We present evidence that our approach identifies key regulators of cell identity in the human adult pancreas. We predict that HEYL and JUND are active in acinar and alpha cells, respectively, and show that these proteins are present in the human adult pancreas as well as in human induced pluripotent stem cell-derived pancreatic cells. The comprehensive gene regulatory network atlas can be explored interactively online. We anticipate our analysis to be the starting point for a more sophisticated dissection of how transcription factors regulate cell identity in the human adult pancreas. Furthermore, given that transcription factors are major regulators of embryo development and are often perturbed in diseases, a comprehensive understanding of how transcription factors work will be relevant in development and disease biology.HIGHLIGHTS-Reconstruction of gene regulatory networks for human adult pancreatic cell types-An interactive resource to explore and visualize gene expression and regulatory states-Predicting putative transcription factors driving pancreatic cell identity-HEYL and JUND as candidate regulators of acinar and alpha cell identity, respectively

scholarly journals A comparative analytical assay of gene regulatory networks inferred using microarray and RNA-seq datasets

2016 ◽  
Vol 12 (06) ◽  
pp. 340-341 ◽  
Author(s):  
Fereshteh Izadi ◽  
◽  
Hamid Najafi Zarrini ◽  
Nadali Babaeian Jelodar ◽  
◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Rna Seq ◽  
Gene Regulatory ◽  
Analytical Assay

scholarly journals Cell-free gene-regulatory network engineering with synthetic transcription factors

2019 ◽  
Vol 116 (13) ◽  
pp. 5892-5901 ◽  
Author(s):  
Zoe Swank ◽  
Nadanai Laohakunakorn ◽  
Sebastian J. Maerkl
Keyword(s):  
Transcription Factors ◽  
High Throughput ◽  
Gene Regulatory Networks ◽  
Protein Interactions ◽  
Transcriptional Repression ◽  
Regulatory Networks ◽  
De Novo ◽  
Mechanistic Modeling ◽  
Free System ◽  
Gene Regulatory

Gene-regulatory networks are ubiquitous in nature and critical for bottom-up engineering of synthetic networks. Transcriptional repression is a fundamental function that can be tuned at the level of DNA, protein, and cooperative protein–protein interactions, necessitating high-throughput experimental approaches for in-depth characterization. Here, we used a cell-free system in combination with a high-throughput microfluidic device to comprehensively study the different tuning mechanisms of a synthetic zinc-finger repressor library, whose affinity and cooperativity can be rationally engineered. The device is integrated into a comprehensive workflow that includes determination of transcription-factor binding-energy landscapes and mechanistic modeling, enabling us to generate a library of well-characterized synthetic transcription factors and corresponding promoters, which we then used to build gene-regulatory networks de novo. The well-characterized synthetic parts and insights gained should be useful for rationally engineering gene-regulatory networks and for studying the biophysics of transcriptional regulation.

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