scholarly journals Functional divergence of paralogous transcription factors supported the evolution of biomineralization in echinoderms

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jian Ming Khor ◽  
Charles A Ettensohn
Keyword(s):  
Transcription Factor ◽  
Regulatory Network ◽  
Function Analysis ◽  
Functional Divergence ◽  
Duplication Event ◽  
Functional Specialization ◽  
Gene Duplication Event ◽  
Morphological Novelty ◽  
Gene Regulatory ◽  
And Function

Alx1 is a pivotal transcription factor in a gene regulatory network that controls skeletogenesis throughout the echinoderm phylum. We performed a structure-function analysis of sea urchin Alx1 using a rescue assay and identified a novel, conserved motif (Domain 2) essential for skeletogenic function. The paralogue of Alx1, Alx4, was not functionally interchangeable with Alx1, but insertion of Domain 2 conferred robust skeletogenic function on Alx4. We used cross-species expression experiments to show that Alx1 proteins from distantly related echinoderms are not interchangeable, although the sequence and function of Domain 2 are highly conserved. We also found that Domain 2 is subject to alternative splicing and provide evidence that this domain was originally gained through exonization. Our findings show that a gene duplication event permitted the functional specialization of a transcription factor through changes in exon-intron organization and thereby supported the evolution of a major morphological novelty.

Deciphering the transcription factor-microRNA-target gene regulatory network associated with graphene oxide cytotoxicity

2018 ◽  
Vol 12 (9) ◽  
pp. 1014-1026 ◽  
Author(s):  
Masoumeh Farahani ◽  
Mostafa Rezaei–Tavirani ◽  
Hakimeh Zali ◽  
Afsaneh Arefi Oskouie ◽  
Meisam Omidi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Graphene Oxide ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Target Gene ◽  
Microrna Target ◽  
Gene Regulatory

scholarly journals Tfap2a is a novel gatekeeper of differentiation in renal progenitors during kidney development

2018 ◽  
Author(s):  
Brooke E. Chambers ◽  
Gary F. Gerlach ◽  
Karen H. Chen ◽  
Eleanor G. Clark ◽  
Ignaty Leshchiner ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genetic Control ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Kidney Development ◽  
Distal Segment ◽  
Distal Nephron ◽  
Nephron Segment ◽  
Gene Regulatory ◽  
First Time

AbstractRenal functional units known as nephrons undergo patterning events during development that create a segmental array of cellular populations with discrete physiological tasks. Knowledge about the terminal differentiation programs of each nephron segment has central importance for understanding kidney disease and to advance regenerative medicine, as mammalian nephrons grown in organoid cultures from pluripotent cells fail to terminally differentiate. Here, from a novel forward genetic screen using zebrafish we report the discovery that transcription factor AP-2 alpha (tfap2a) coordinates a gene regulatory network that controls the progression of nephron distal segment progenitors into the differentiated state. Overexpression of tfap2a rescued differentiation in mutants and caused ectopic expression of distal segment markers in wild-type nephrons, indicating tfap2a is sufficient to instigate the distal segment differentiation program. tfap2a/2b deficiency exacerbated distal nephron segment differentiation defects, revealing functional redundancy where tfap2a has a dominant role upstream of its family member. With further genetic studies, we assembled a blueprint of the tfap2a gene regulatory network during nephrogenesis. We demonstrate that tfap2a acts downstream of Iroquois homeobox 3b, a conserved distal lineage transcription factor. tfap2a controls a circuit consisting of irx1a, tfap2b, and genes encoding solute transporters that dictate the specialized metabolic functions of the distal nephron segments, and we show for the first time that this regulatory node is distinct from the pathway circuits controlling aspects such as apical-basal polarity and ciliogenesis during the differentiation process. Thus, our studies reveal new insights into the genetic control of differentiation, where tfap2a regulates the suite of segment transporter traits. These findings have relevance for understanding renal birth defects, as well as efforts to recapitulate nephrogenesis in vivo to make functional units that can facilitate organoid applications such as drug discovery and regenerative therapies.Summary StatementHere, we report for the first time that transcription factor AP-2 alpha (tfap2a) controls the progression from nephron progenitor into the fully differentiated state. This fundamentally deepens our knowledge about the genetic control of kidney development.

scholarly journals Characterisation of the Genes Encoding Mannuronan-C5-Epimerase in the Brown Alga Lessonia Variegata

2021 ◽  
Author(s):  
◽  
Sayani Ghosh
Keyword(s):  
Brown Alga ◽  
Sequence Variation ◽  
Saccharina Japonica ◽  
Duplication Event ◽  
Biochemical Pathway ◽  
Gene Duplication Event ◽  
Laminaria Digitata ◽  
Coding Region ◽  
Genes Encoding ◽  
And Function

<p>Alginate is known to be a commercially valuable polysaccharide, of great importance in industries such as food, cosmetics, medicine and pharmaceuticals. It is obtained commercially by harvesting brown algae. The final step in the alginate biochemical pathway involves the epimerization of D-mannuronic residues into L-guluronic residues, catalyzed by the enzyme mannuronan-C5-epimerase. This final step has been found to be responsible for controlling the physicochemical properties of the produced alginate. This study is the first to characterize the genes encoding for the enzyme mannuronan-C5- epimerase in the Northern, Southern and Wellington lineages of the brown alga Lessonia variegata (Phaeophyceae). The gene of interest was amplified by standard PCR and cloning. Cloning PCR results revealed the presence of two distinct copies of the gene in Lessonia variegata. The coding region of the copies was found to be very conserved with very little sequence variation. The Lessonia variegata sequences were compared with those of Laminaria digitata and Saccharina japonica, which indicated that at least one gene duplication event has occurred in Lessonia variegata, leading to the formation of two gene duplicates. The possible mechanisms by which the gene paralogs may control the structure and function of the produced alginate have been discussed.</p>

scholarly journals Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

2020 ◽  
Author(s):  
Maud Fagny ◽  
Marieke Lydia Kuijjer ◽  
Maike Stam ◽  
Johann Joets ◽  
Olivier Turc ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Sites ◽  
Regulatory Network ◽  
Tissue Specificity ◽  
Target Genes ◽  
Specific Gene ◽  
Tissue Specific ◽  
Genome Wide ◽  
Gene Regulatory

AbstractEnhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity.SignificanceEnhancers play a major role in regulating tissue-specific gene expression in higher eukaryotes, including angiosperms. While molecular characterization of enhancers has improved over the past years, identifying their target genes at the genome-wide scale remains challenging. Here, we integrate genomic, epigenomic and transcriptomic data to decipher the tissue-specific gene regulatory network controlled by enhancers at two different stages of maize leaf development. Using a systems biology approach, we identify transcription factor families regulating gene tissue-specific expression in husk and seedling leaves, and characterize the enhancers likely to be involved. We show that a large part of maize enhancers is derived from transposable elements, which can provide novel transcription factor binding sites crucial to the regulation of tissue-specific biological functions.

scholarly journals The transcription factor Zic4 acts as a transdifferentiation switch

2021 ◽  
Author(s):  
Matthias Christian Vogg ◽  
Jaroslav Ferenc ◽  
Wanda Christa Buzgariu ◽  
Chrystelle Perruchoud ◽  
Panagiotis Papasaikas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Gene Regulatory Network ◽  
Cell Fate ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Model System ◽  
Cell Identity ◽  
Transcriptional Switch ◽  
Gene Regulatory

The molecular mechanisms that maintain cell identities and prevent transdifferentiation remain mysterious. Interestingly, both dedifferentiation and transdifferentiation are transiently reshuffled during regeneration. Therefore, organisms that regenerate readily offer a fruitful paradigm to investigate the regulation of cell fate stability. Here, we used Hydra as a model system and show that Zic4 silencing is sufficient to induce transdifferentiation of tentacle into foot cells. We identified a Wnt-controlled Gene Regulatory Network that controls a transcriptional switch of cell identity. Furthermore, we show that this switch also controls the re-entry into the cell cycle. Our data indicate that maintenance of cell fate by a Wnt-controlled GRN is a key mechanism during both homeostasis and regeneration.

scholarly journals Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Carine Gubelmann ◽  
Petra C Schwalie ◽  
Sunil K Raghav ◽  
Eva Röder ◽  
Tenagne Delessa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Whole Body ◽  
Central Component ◽  
Fat Cell ◽  
Differentiation Potential ◽  
Adipogenic Gene ◽  
Gene Regulatory

Adipose tissue is a key determinant of whole body metabolism and energy homeostasis. Unraveling the regulatory mechanisms underlying adipogenesis is therefore highly relevant from a biomedical perspective. Our current understanding of fat cell differentiation is centered on the transcriptional cascades driven by the C/EBP protein family and the master regulator PPARγ. To elucidate further components of the adipogenic gene regulatory network, we performed a large-scale transcription factor (TF) screen overexpressing 734 TFs in mouse pre-adipocytes and probed their effect on differentiation. We identified 22 novel pro-adipogenic TFs and characterized the top ranking TF, ZEB1, as being essential for adipogenesis both in vitro and in vivo. Moreover, its expression levels correlate with fat cell differentiation potential in humans. Genomic profiling further revealed that this TF directly targets and controls the expression of most early and late adipogenic regulators, identifying ZEB1 as a central transcriptional component of fat cell differentiation.

scholarly journals Genome-wide identification of long non-coding RNA targets of the tomato MADS box transcription factor RIN and function analysis

2018 ◽  
Vol 123 (3) ◽  
pp. 469-482 ◽  
Author(s):  
Tongtong Yu ◽  
David T W Tzeng ◽  
Ran Li ◽  
Jianye Chen ◽  
Silin Zhong ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Function Analysis ◽  
Mads Box ◽  
Non Coding Rna ◽  
Rna Targets ◽  
Genome Wide ◽  
And Function ◽  
Long Non Coding Rna

scholarly journals A gene regulatory network controlled by the NAC transcription factor ANAC092/AtNAC2/ORE1 during salt-promoted senescence

2010 ◽  
Vol 62 (2) ◽  
pp. 250-264 ◽  
Author(s):  
Salma Balazadeh ◽  
Hamad Siddiqui ◽  
Annapurna D. Allu ◽  
Lilian P. Matallana-Ramirez ◽  
Camila Caldana ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Nac Transcription Factor ◽  
Gene Regulatory

scholarly journals The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation

2015 ◽  
Vol 26 (20) ◽  
pp. 3615-3627 ◽  
Author(s):  
Cécile Sauvanet ◽  
Damien Garbett ◽  
Anthony Bretscher
Keyword(s):  
Pdz Domain ◽  
Duplication Event ◽  
Scaffolding Protein ◽  
Gene Duplication Event ◽  
Pdz Domains ◽  
Tail Region ◽  
Dynamics And Function ◽  
And Function

We examine the dynamics and function of the apical scaffolding protein E3KARP/NHERF2, which consists of two PDZ domains and a tail containing an ezrin-binding domain. The exchange rate of E3KARP is greatly enhanced during mitosis due to phosphorylation at Ser-303 in its tail region. Whereas E3KARP can substitute for the function of the closely related scaffolding protein EBP50/NHERF1 in the formation of interphase microvilli, E3KARP S303D cannot. Moreover, the S303D mutation enhances the in vivo dynamics of the E3KARP tail alone, whereas in vitro the interaction of E3KARP with active ezrin is unaffected by S303D, implicating another factor regulating dynamics in vivo. A-Raf is found to be required for S303 phosphorylation in mitotic cells. Regulation of the dynamics of EBP50 is known to be dependent on its tail region but modulated by PDZ domain occupancy, which is not the case for E3KARP. Of interest, in both cases, the mechanisms regulating dynamics involve the tails, which are the most diverged region of the paralogues and probably evolved independently after a gene duplication event that occurred early in vertebrate evolution.

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