scholarly journals osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

Development ◽  
2021 ◽  
Author(s):  
Elliot A. Perens ◽  
Jessyka T. Diaz ◽  
Agathe Quesnel ◽  
Amjad Askary ◽  
J. Gage Crump ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Bhlh Transcription Factor ◽  
Transcriptional Regulatory Networks ◽  
Mesoderm Cell ◽  
Intermediate Mesoderm ◽  
Transcriptional Regulatory ◽  
Mutant Phenotypes

Transcriptional regulatory networks refine gene expression boundaries to define the dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and neighboring vessel progenitors are poorly understood. Here, we delineate roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses osr1 mutant phenotypes. hand2 and osr1 are expressed together in the posterior mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 during this timeframe inhibits LVP development while enhancing IM formation and can rescue the osr1 mutant phenotype. Together, our data demonstrate that osr1 modulates the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the kidney and vessel progenitor territories.

scholarly journals osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

2020 ◽  
Author(s):  
Elliot A. Perens ◽  
Jessyka T. Diaz ◽  
Agathe Quesnel ◽  
Amjad Askary ◽  
J. Gage Crump ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Bhlh Transcription Factor ◽  
Transcriptional Regulatory Networks ◽  
Mesoderm Cell ◽  
Intermediate Mesoderm ◽  
Transcriptional Regulatory ◽  
Mutant Phenotypes

ABSTRACTTranscriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood. Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses the osr1 mutant phenotypes. hand2 and osr1 are both expressed in the posterior lateral mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 inhibits LVP development while enhancing IM formation. Together, our data demonstrate that osr1 modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the dimensions of kidney and vessel progenitor territories.SUMMARY STATEMENTAnalysis of the osr1 mutant phenotype reveals roles in determining the extent of intermediate mesoderm formation while inhibiting premature differentiation of neighboring vessel progenitors.

scholarly journals Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Elliot A Perens ◽  
Zayra V Garavito-Aguilar ◽  
Gina P Guio-Vega ◽  
Karen T Peña ◽  
Yocheved L Schindler ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Zinc Finger ◽  
Kidney Development ◽  
Bhlh Transcription Factor ◽  
Lateral Boundary ◽  
Zinc Finger Transcription Factor ◽  
Cell Fate Decisions ◽  
Intermediate Mesoderm ◽  
Vein Formation

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.

scholarly journals Hand2 Inhibits Kidney Specification While Promoting Vein Formation Within the Posterior Mesoderm

2016 ◽  
Author(s):  
Elliot A. Perens ◽  
Zayra V. Garavito-Aguilar ◽  
Gina P. Guio-Vega ◽  
Karen T. Peña ◽  
Yocheved L. Schindler ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Zinc Finger ◽  
Kidney Development ◽  
Bhlh Transcription Factor ◽  
Lateral Boundary ◽  
Zinc Finger Transcription Factor ◽  
Cell Fate Decisions ◽  
Intermediate Mesoderm ◽  
Vein Formation

AbstractProper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidneyby restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.IMPACT STATEMENTThe Hand2 transcription factor regulates the dimensions of the kidney by controlling cell fate decisions at the interface between organ fields.

Genome-Wide Transcriptional Regulatory Networks Downstream of TAL1/SCL in T-Cell Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 416-416 ◽  
Author(s):  
Teresa Palomero ◽  
Duncan T. Odom ◽  
Jennifer O’Neil ◽  
Adolfo A. Ferrando ◽  
Stuart S. Winter ◽  
...  
Keyword(s):  
Transcription Factor ◽  
T Cell ◽  
Regulatory Networks ◽  
Lymphoblastic Leukemia ◽  
E Proteins ◽  
Promoter Regions ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Cell Acute Lymphoblastic Leukemia ◽  
On Chip

Abstract Aberrant expression of transcription factor oncogenes is a common feature in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), however, oncogenic transcriptional programs downstream of T-ALL oncogenes are mostly unknown. We used chromatin immunoprecipitation combined with promoter microarrays (ChIP on chip) to identify direct transcriptional targets of TAL1/SCL, a bHLH transcription factor aberrantly expressed in 60% of patients with T-ALL. Using the Hu12K arrays that contain over 12,000 human promoter regions, we have identified 71 direct targets of TAL1 in the Jurkat T-ALL cell line by ChIP on chip, and have been able to validate 80% of them by conventional chromatin immunoprecipitation followed by quantitative real time PCR. It has previously been demonstrated that TAL1 needs to bind to E proteins (E2A, HEB or E2-2) to achieve an efficient interaction with DNA. We verified that promoters occupied by TAL1 are bound by both the E-proteins E2A and HEB in at least 50% of TAL1-bound promoter regions, suggesting that TAL1/E2A as well as TAL1/HEB heterodimers play a role in the transformation of T-cell precursors. Using RNA interference to knock down TAL1, we have demonstrated functional regulation through TAL1-binding of a significant percentage of the targets identified by ChIP on chip. Results demonstrate that some TAL1 direct targets are repressed by the binding of this transcription factor, while others seem to be activated or are not altered, indicating a high level of complexity in the organization of TAL1-mediated transcriptional regulatory networks. Also, specific association of the expression levels of TAL1 targets in TAL1 positive primary leukemia samples has been shown by comparing gene expression arrays from the different T-ALL subsets. Our results indicate that TAL1 acts as a master transcriptional regulator at the top of a complex regulatory network that contributes to leukemogenesis by regulating T-cell differentiation, proliferation and survival.

scholarly journals CoryneRegNet 2: An Integrative Bioinformatics Approach for Reconstruction and Comparison of Transcriptional Regulatory Networks in Prokaryotes

2006 ◽  
Vol 3 (2) ◽  
pp. 1-13 ◽  
Author(s):  
Jan Baumbach ◽  
Karina Brinkrolf ◽  
Tobias Wittkop ◽  
Andreas Tauch ◽  
Sven Rahmann
Keyword(s):  
Transcription Factor ◽  
Data Warehouse ◽  
Binding Sites ◽  
Regulatory Network ◽  
High Performance ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Search Tool ◽  
Gene Regulatory

SummaryCoryneRegNet is an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. Initially, it was designed to provide methods for the analysis and visualization of the gene regulatory network of Corynebacterium glutamicum. Now we integrated the genomes and transcriptional interactions of three other corynebacteria, C. diphtheriae, C. efficiens, and C. jeikeium into CoryneRegNet; providing comparative analysis and visualization with GraphVis. We also integrated the high-performance PSSM search tool PoSSuM search to detect potential transcription factor binding sites within and across species. As an application, we reconstruct in silico the regulatory network of the iron metabolism regulator DtxR in the four corynebacteria.CoryneRegNet is freely accessible at https://www.cebitec.uni-bielefeld.de/groups/gi/software/coryneregnet/. The final slash (/) is mandatory. In order to use the GraphVis feature, Java (at least version 1.4.2) is required.

scholarly journals Unraveling the functions of uncharacterized transcription factors in Escherichia coli using ChIP-exo

2021 ◽  
Author(s):  
Ye Gao ◽  
Hyun Gyu Lim ◽  
Hans Verkler ◽  
Richard Szubin ◽  
Daniel Quach ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Transcription Factors ◽  
Dna Binding ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Cellular Processes ◽  
Transcriptional Regulatory ◽  
Mutant Phenotypes ◽  
K 12

Bacteria regulate gene expression to adapt to changing environments through transcriptional regulatory networks (TRNs). Although extensively studied, no TRN is fully characterized since the identity and activity of all the transcriptional regulators that comprise a TRN are not known. Here, we experimentally evaluate 40 uncharacterized proteins in Escherichia coli K-12 MG1655, which were computationally predicted to be transcription factors (TFs). First, we used a multiplexed ChIP-exo assay to characterize genome-wide binding sites for these candidate TFs; 34 of them were found to be DNA-binding protein. We then compared the relative location between binding sites and RNA polymerase (RNAP). We found 48% (283/588) overlap between the TFs and RNAP. Finally, we used these data to infer potential functions for 10 of the 34 TFs with validated DNA binding sites and consensus binding motifs. These TFs were found to have various roles in regulating primary cellular processes in E. coli. Taken together, this study: (1) significantly expands the number of confirmed TFs, close to the estimated total of about 280 TFs; (2) predicts the putative functions of the newly discovered TFs, and (3) confirms the functions of representative TFs through mutant phenotypes.

Systematic genetic analysis of transcription factors to map the fission yeast transcription-regulatory network

2013 ◽  
Vol 41 (6) ◽  
pp. 1696-1700 ◽  
Author(s):  
Gordon Chua
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Fission Yeast ◽  
Regulatory Networks ◽  
Target Genes ◽  
Transcriptome Profiling ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Transcription Factor Genes ◽  
Almost All

Mapping transcriptional-regulatory networks requires the identification of target genes, binding specificities and signalling pathways of transcription factors. However, the characterization of each transcription factor sufficiently for deciphering such networks remains laborious. The recent availability of overexpression and deletion strains for almost all of the transcription factor genes in the fission yeast Schizosaccharomyces pombe provides a valuable resource to better investigate transcription factors using systematic genetics. In the present paper, I review and discuss the utility of these strain collections combined with transcriptome profiling and genome-wide chromatin immunoprecipitation to identify the target genes of transcription factors.

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