scholarly journals Genome-wide discovery of the daily transcriptome, DNA regulatory elements and transcription factor occupancy in the monarch butterfly brain

PLoS Genetics ◽  
2019 ◽  
Vol 15 (7) ◽  
pp. e1008265 ◽  
Author(s):  
Aldrin B. Lugena ◽  
Ying Zhang ◽  
Jerome S. Menet ◽  
Christine Merlin
Keyword(s):  
Transcription Factor ◽  
Monarch Butterfly ◽  
Regulatory Elements ◽  
Genome Wide ◽  
Dna Regulatory Elements ◽  
Transcription Factor Occupancy

scholarly journals The native cistrome and sequence motif families of the maize ear

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009689
Author(s):  
Savannah D. Savadel ◽  
Thomas Hartwig ◽  
Zachary M. Turpin ◽  
Daniel L. Vera ◽  
Pei-Yau Lung ◽  
...  
Keyword(s):  
High Resolution ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Regulatory Elements ◽  
Chromatin Interaction ◽  
Sequence Motif ◽  
Binding Prediction ◽  
Interaction Sites ◽  
Genome Wide ◽  
Dna Regulatory Elements

Elucidating the transcriptional regulatory networks that underlie growth and development requires robust ways to define the complete set of transcription factor (TF) binding sites. Although TF-binding sites are known to be generally located within accessible chromatin regions (ACRs), pinpointing these DNA regulatory elements globally remains challenging. Current approaches primarily identify binding sites for a single TF (e.g. ChIP-seq), or globally detect ACRs but lack the resolution to consistently define TF-binding sites (e.g. DNAse-seq, ATAC-seq). To address this challenge, we developed MNase-defined cistrome-Occupancy Analysis (MOA-seq), a high-resolution (< 30 bp), high-throughput, and genome-wide strategy to globally identify putative TF-binding sites within ACRs. We used MOA-seq on developing maize ears as a proof of concept, able to define a cistrome of 145,000 MOA footprints (MFs). While a substantial majority (76%) of the known ATAC-seq ACRs intersected with the MFs, only a minority of MFs overlapped with the ATAC peaks, indicating that the majority of MFs were novel and not detected by ATAC-seq. MFs were associated with promoters and significantly enriched for TF-binding and long-range chromatin interaction sites, including for the well-characterized FASCIATED EAR4, KNOTTED1, and TEOSINTE BRANCHED1. Importantly, the MOA-seq strategy improved the spatial resolution of TF-binding prediction and allowed us to identify 215 motif families collectively distributed over more than 100,000 non-overlapping, putatively-occupied binding sites across the genome. Our study presents a simple, efficient, and high-resolution approach to identify putative TF footprints and binding motifs genome-wide, to ultimately define a native cistrome atlas.

scholarly journals Genomic Characterization of Endothelial Enhancers Reveals a Multifunctional Role for NR2F2 in Regulation of Arteriovenous Gene Expression

2020 ◽  
Vol 126 (7) ◽  
pp. 875-888 ◽  
Author(s):  
Samir Sissaoui ◽  
Jun Yu ◽  
Aimin Yan ◽  
Rui Li ◽  
Onur Yukselen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Transcription Factor ◽  
Deep Sequencing ◽  
Chromatin Immunoprecipitation ◽  
Regulatory Elements ◽  
Bhlh Transcription Factor ◽  
Genome Wide ◽  
A Genome

Rationale: Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap. Objective: To identify and characterize artery- and vein-specific endothelial enhancers in the human genome, thereby gaining insights into mechanisms by which blood vessel identity is regulated. Methods and Results: Using chromatin immunoprecipitation and deep sequencing for markers of active chromatin in human arterial and venous endothelial cells, we identified several thousand artery- and vein-specific regulatory elements. Computational analysis revealed that NR2F2 (nuclear receptor subfamily 2, group F, member 2) sites were overrepresented in vein-specific enhancers, suggesting a direct role in promoting vein identity. Subsequent integration of chromatin immunoprecipitation and deep sequencing data sets with RNA sequencing revealed that NR2F2 regulated 3 distinct aspects related to arteriovenous identity. First, consistent with previous genetic observations, NR2F2 directly activated enhancer elements flanking cell cycle genes to drive their expression. Second, NR2F2 was essential to directly activate vein-specific enhancers and their associated genes. Our genomic approach further revealed that NR2F2 acts with ERG (ETS-related gene) at many of these sites to drive vein-specific gene expression. Finally, NR2F2 directly repressed only a small number of artery enhancers in venous cells to prevent their activation, including a distal element upstream of the artery-specific transcription factor, HEY2 (hes related family bHLH transcription factor with YRPW motif 2). In arterial endothelial cells, this enhancer was normally bound by ERG, which was also required for arterial HEY2 expression. By contrast, in venous endothelial cells, NR2F2 was bound to this site, together with ERG, and prevented its activation. Conclusions: By leveraging a genome-wide approach, we revealed mechanistic insights into how NR2F2 functions in multiple roles to maintain venous identity. Importantly, characterization of its role at a crucial artery enhancer upstream of HEY2 established a novel mechanism by which artery-specific expression can be achieved.

scholarly journals The transcription factor GLI1 cooperates with the chromatin remodeler SMARCA2 to regulate chromatin accessibility at distal DNA regulatory elements

2020 ◽  
Vol 295 (26) ◽  
pp. 8725-8735
Author(s):  
Stephanie L. Safgren ◽  
Rachel L. O. Olson ◽  
Anne M. Vrabel ◽  
Luciana L. Almada ◽  
David L. Marks ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Micrococcal Nuclease ◽  
Gene Promoters ◽  
Interacting Protein ◽  
Transcriptional Activation Domain ◽  
Dna Regulatory Elements

The transcription factor GLI1 (GLI family zinc finger 1) plays a key role in the development and progression of multiple malignancies. To date, regulation of transcriptional activity at target gene promoters is the only molecular event known to underlie the oncogenic function of GLI1. Here, we provide evidence that GLI1 controls chromatin accessibility at distal regulatory regions by modulating the recruitment of SMARCA2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2) to these elements. We demonstrate that SMARCA2 endogenously interacts with GLI1 and enhances its transcriptional activity. Mapping experiments indicated that the C-terminal transcriptional activation domain of GLI1 and SMARCA2's central domains, including its ATPase motif, are required for this interaction. Interestingly, similar to SMARCA2, GLI1 overexpression increased chromatin accessibility, as indicated by results of the micrococcal nuclease assay. Further, results of assays for transposase-accessible chromatin with sequencing (ATAC-seq) after GLI1 knockdown supported these findings, revealing that GLI1 regulates chromatin accessibility at several regions distal to gene promoters. Integrated RNA-seq and ATAC-seq data analyses identified a subset of differentially expressed genes located in cis to these regulated chromatin sites. Finally, using the GLI1-regulated gene HHIP (Hedgehog-interacting protein) as a model, we demonstrate that GLI1 and SMARCA2 co-occupy a distal chromatin peak and that SMARCA2 recruitment to this HHIP putative enhancer requires intact GLI1. These findings provide insights into how GLI1 controls gene expression in cancer cells and may inform approaches targeting this oncogenic transcription factor to manage malignancies.

scholarly journals DNA specificities modulate the binding of human transcription factor A to mitochondrial DNA control region

2019 ◽  
Vol 47 (12) ◽  
pp. 6519-6537
Author(s):  
Anna Cuppari ◽  
Pablo Fernández-Millán ◽  
Federica Battistini ◽  
Aleix Tarrés-Solé ◽  
Sébastien Lyonnais ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mitochondrial Dna ◽  
Control Region ◽  
Regulatory Elements ◽  
High Concentration ◽  
Mitochondrial Dna Control Region ◽  
Oxidative Phosphorylation Pathway ◽  
Dna Regulatory Elements ◽  
Dna Complex ◽  
Transcription And Replication

Abstract Human mitochondrial DNA (h-mtDNA) codes for 13 subunits of the oxidative phosphorylation pathway, the essential route that produces ATP. H-mtDNA transcription and replication depends on the transcription factor TFAM, which also maintains and compacts this genome. It is well-established that TFAM activates the mtDNA promoters LSP and HSP1 at the mtDNA control region where DNA regulatory elements cluster. Previous studies identified still uncharacterized, additional binding sites at the control region downstream from and slightly similar to LSP, namely sequences X and Y (Site-X and Site-Y) (Fisher et al., Cell 50, pp 247–258, 1987). Here, we explore TFAM binding at these two sites and compare them to LSP by multiple experimental and in silico methods. Our results show that TFAM binding is strongly modulated by the sequence-dependent properties of Site-X, Site-Y and LSP. The high binding versatility of Site-Y or the considerable stiffness of Site-X tune TFAM interactions. In addition, we show that increase in TFAM/DNA complex concentration induces multimerization, which at a very high concentration triggers disruption of preformed complexes. Therefore, our results suggest that mtDNA sequences induce non-uniform TFAM binding and, consequently, direct an uneven distribution of TFAM aggregation sites during the essential process of mtDNA compaction.

scholarly journals Gene regulation gravitates towards either addition or multiplication when combining the effects of two signals

2020 ◽  
Author(s):  
Eric M. Sanford ◽  
Benjamin L. Emert ◽  
Allison Coté ◽  
Arjun Raj
Keyword(s):  
Transcriptional Response ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Mechanistic Models ◽  
Transcriptional Responses ◽  
Genome Wide ◽  
Putative Transcription Factor ◽  
The Individual ◽  
Transcription Factor Occupancy ◽  
Mcf 7

AbstractSignals often ultimately affect the transcription of genes, and often, two different signals can affect the transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. Mechanistic models can predict a range of combined responses, with the most commonly applied models predicting additive or multiplicative responses, but systematic genome-wide evaluation of these predictions are not available. Here, we performed a comprehensive analysis of the transcriptional response of human MCF-7 cells to two different signals (retinoic acid and TGF-β), applied individually and in combination. We found that the combined responses exhibited a range of behaviors, but clearly favored both additive and multiplicative combined transcriptional responses. We also performed paired chromatin accessibility measurements to measure putative transcription factor occupancy at regulatory elements near these genes. We found that increases in chromatin accessibility were largely additive, meaning that the combined accessibility response was the sum of the accessibility responses to each signal individually. We found some association between super-additivity of accessibility and multiplicative or super-multiplicative combined transcriptional responses, while sub-additivity of accessibility associated with additive transcriptional responses. Our findings suggest that mechanistic models of combined transcriptional regulation must be able to reproduce a range of behaviors.

scholarly journals Genome-wide identification, expression and bioinformatic analyses of GRAS transcription factor genes in rice

2021 ◽  
Author(s):  
Mouboni Dutta ◽  
Anusree Saha ◽  
Mazahar Moin ◽  
P B Kirti
Keyword(s):  
Transcription Factor ◽  
Stress Tolerance ◽  
Rice Variety ◽  
Expression Patterns ◽  
Functional Characterization ◽  
Regulatory Elements ◽  
Sheath Blight ◽  
Gras Transcription Factor ◽  
Genome Wide ◽  
In Silico Studies

Our group has previously identified the activation tagging of a GRAS transcription factor (TF)gene in the gain-of-function mutant population of rice (indica rice variety BPT 5204) screened for water use efficiency (Moin et al, 2016a). This family of GRAS transcription factors has been well known for their diverse roles in gibberellin signaling, light responses, root development, gametogenesis etc. Recent studies indicated their role in biotic and abiotic responses as well. Although this family of TFs received significant attention, not many genes were identified specifically for their roles in mediating stress tolerance in rice. Only OsGRAS23 (here named as OsGRAS22) was reported to code for a TF that induces drought tolerance in rice. In the present study, we have analyzed the expression patterns of rice GRAS TF genes under abiotic (NaCl and ABA treatments) and biotic (leaf samples infected with pathogens, Xanthomonas oryzae pv. oryzae that causes bacterial leaf blight and Rhizoctonia solani that causes sheath blight) stress conditions. In addition, their expression patterns were also analyzed in thirteen different developmental stages. We studied their spatio-temporal regulation and correlated them with in-silico studies. Fully annotated genomic sequences available in rice database have enabled us to study the protein properties, ligand interactions, domain analysis and presence of cis-regulatory elements in a bioinformatics analysis. Most of the genes were induced immediately after the onset of stress particularly in the roots of ABA treated plants. OsGRAS39 was found to be very highly expressive gene under sheath blight infection and both abiotic stress treatments while OsGRAS8, OsSHR1 and OsSLR1 were also responsive. Our earlier functional characterization (Moin et al., 2016a) followed by the genome wide characterization of the GRAS gene family members in the present study clearly show that they are highly appropriate candidate genes for manipulating stress tolerance in rice and other crop plants.

Sign in / Sign up

Export Citation Format

Share Document