scholarly journals Primate-specific stress-induced transcription factor POU2F1Z protects human neuronal cells from stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander G. Stepchenko ◽  
Tatiana N. Portseva ◽  
Ivan A. Glukhov ◽  
Alina P. Kotnova ◽  
Bella M. Lyanova ◽  
...  

AbstractThe emergence of new primate-specific genes is an essential factor in human and primate brain development and functioning. POU2F1/Oct-1 is a transcription regulator in higher eukaryotes which is involved in the regulation of development, differentiation, stress response, and other processes. We have demonstrated that the Tigger2 transposon insertion into the POU2F1 gene which occurred in the primate lineage led to the formation of an additional exon (designated the Z-exon). Z-exon-containing primate-specific Oct-1Z transcript includes a short upstream ORF (uORF) located at its 5’-end and the main ORF encoding the Oct-1Z protein isoform (Pou2F1 isoform 3, P14859-3), which differs from other Oct-1 isoforms by its N-terminal peptide. The Oct-1Z-encoding transcript is expressed mainly in human brain cortex. Under normal conditions, the translation of the ORF coding for the Oct-1Z isoform is repressed by uORF. Under various stress conditions, uORF enables a strong increase in the translation of the Oct-1Z-encoding ORF. Increased Oct-1Z expression levels in differentiating human neuroblasts activate genes controlling stress response, neural cell differentiation, brain formation, and organogenesis. We have shown that the Oct-1Z isoform of the POU2F1/Oct-1 transcription factor is an example of a primate-specific genomic element contributing to brain development and cellular stress defense.

2021 ◽  
Vol 22 (13) ◽  
pp. 6952
Author(s):  
Mingxin Yu ◽  
Junling Liu ◽  
Bingshuai Du ◽  
Mengjuan Zhang ◽  
Aibin Wang ◽  
...  

NAC (NAM, ATAF1/2, and CUC2) transcription factors are ubiquitously distributed in eukaryotes and play significant roles in stress response. However, the functional verifications of NACs in Picea (P.) wilsonii remain largely uncharacterized. Here, we identified the NAC transcription factor PwNAC11 as a mediator of drought stress, which was significantly upregulated in P. wilsonii under drought and abscisic acid (ABA) treatments. Yeast two-hybrid assays showed that both the full length and C-terminal of PwNAC11 had transcriptional activation activity and PwNAC11 protein cannot form a homodimer by itself. Subcellular observation demonstrated that PwNAC11 protein was located in nucleus. The overexpression of PwNAC11 in Arabidopsis obviously improved the tolerance to drought stress but delayed flowering time under nonstress conditions. The steady-state level of antioxidant enzymes’ activities and light energy conversion efficiency were significantly increased in PwNAC11 transgenic lines under dehydration compared to wild plants. PwNAC11 transgenic lines showed hypersensitivity to ABA and PwNAC11 activated the expression of the downstream gene ERD1 by binding to ABA-responsive elements (ABREs) instead of drought-responsive elements (DREs). Genetic evidence demonstrated that PwNAC11 physically interacted with an ABA-induced protein—ABRE Binding Factor3 (ABF3)—and promoted the activation of ERD1 promoter, which implied an ABA-dependent signaling cascade controlled by PwNAC11. In addition, qRT-PCR and yeast assays showed that an ABA-independent gene—DREB2A—was also probably involved in PwNAC11-mediated drought stress response. Taken together, our results provide the evidence that PwNAC11 plays a dominant role in plants positively responding to early drought stress and ABF3 and DREB2A synergistically regulate the expression of ERD1.


2015 ◽  
Vol 28 (1) ◽  
pp. 181-201 ◽  
Author(s):  
Naohiko Ohama ◽  
Kazuya Kusakabe ◽  
Junya Mizoi ◽  
Huimei Zhao ◽  
Satoshi Kidokoro ◽  
...  

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Kyle R. Pomraning ◽  
Erin L. Bredeweg ◽  
Eduard J. Kerkhoven ◽  
Kerrie Barry ◽  
Sajeet Haridas ◽  
...  

ABSTRACTThe yeastYarrowia lipolyticaundergoes a morphological transition from yeast-to-hyphal growth in response to environmental conditions. A forward genetic screen was used to identify mutants that reliably remain in the yeast phase, which were then assessed by whole-genome sequencing. All thesmoothmutants identified, so named because of their colony morphology, exhibit independent loss of DNA at a repetitive locus made up of interspersed ribosomal DNA and short 10- to 40-mer telomere-like repeats. The loss of repetitive DNA is associated with downregulation of genes with stress response elements (5′-CCCCT-3′) and upregulation of genes with cell cycle box (5′-ACGCG-3′) motifs in their promoter region. The stress response element is bound by the transcription factor Msn2p inSaccharomyces cerevisiae. We confirmed that theY. lipolyticamsn2(Ylmsn2) ortholog is required for hyphal growth and found that overexpression of Ylmsn2enables hyphal growth insmoothstrains. The cell cycle box is bound by the Mbp1p/Swi6p complex inS. cerevisiaeto regulate G1-to-S phase progression. We found that overexpression of either the Ylmbp1or Ylswi6homologs decreased hyphal growth and that deletion of either Ylmbp1or Ylswi6promotes hyphal growth insmoothstrains. A second forward genetic screen for reversion to hyphal growth was performed with thesmooth-33mutant to identify additional genetic factors regulating hyphal growth inY. lipolytica. Thirteen of the mutants sequenced from this screen had coding mutations in five kinases, including the histidine kinases Ylchk1and Ylnik1and kinases of the high-osmolarity glycerol response (HOG) mitogen-activated protein (MAP) kinase cascade Ylssk2, Ylpbs2, and Ylhog1. Together, these results demonstrate thatY. lipolyticatransitions to hyphal growth in response to stress through multiple signaling pathways.IMPORTANCEMany yeasts undergo a morphological transition from yeast-to-hyphal growth in response to environmental conditions. We used forward and reverse genetic techniques to identify genes regulating this transition inYarrowia lipolytica. We confirmed that the transcription factor Ylmsn2is required for the transition to hyphal growth and found that signaling by the histidine kinases Ylchk1and Ylnik1as well as the MAP kinases of the HOG pathway (Ylssk2, Ylpbs2, and Ylhog1) regulates the transition to hyphal growth. These results suggest thatY. lipolyticatransitions to hyphal growth in response to stress through multiple kinase pathways. Intriguingly, we found that a repetitive portion of the genome containing telomere-like and rDNA repeats may be involved in the transition to hyphal growth, suggesting a link between this region and the general stress response.


2021 ◽  
Author(s):  
Malalaniaina Rakotobe ◽  
Niels Fjerdingstad ◽  
Nuria Ruiz-Reig ◽  
Thomas Lamonerie ◽  
Fabien D'Autréaux

Abstract Experiencing stress during sensitive periods of brain development has a major impact on how individuals cope with later stress. Although many become more prone to develop anxiety or depression, some appear resilient. The mechanisms underlying these differences are unknown. Key answers may lie in how genetic and environmental stressors interact to shape the circuits controlling emotions. Here we studied the role of the habenulo-interpeducuncular system (HIPS), a critical node of reward circuits, in early stress-induced anxiety. We found that a subcircuit of this system, characterized by Otx2 expression, is particularly responsive to chronic stress during puberty, which induces HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We further show that Otx2 deletion restricted to the HIPS counteracts these effects of stress. Together, these results demonstrate that Otx2 and stress interact, around puberty, to shape the HIPS stress-response, revealed here as a key modulator of susceptibility/resilience to develop anxiety.


2021 ◽  
Author(s):  
Anindita Dutta ◽  
Apurba Das ◽  
Deep Bisht ◽  
Vijendra Arya ◽  
Rohini Muthuswami

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation often implemented by chromatin remodeling proteins.  The study presented in this paper shows that the expression of PICH, an ATP-dependent chromatin remodeler, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response, both in the absence and presence of oxidative stress. In turn, Nrf2 regulates the expression of PICH in the presence of oxidative stress. Both PICH and Nrf2 together regulate the expression of antioxidant genes and this transcriptional regulation is dependent on the ATPase activity of PICH. In addition, H3K27ac modification also plays a role in activating transcription in the presence of oxidative stress. Co-immunoprecipitation experiments show that PICH and Nrf2 interact with H3K27ac in the presence of oxidative stress. Mechanistically, PICH recognizes ARE sequences present on its target genes and introduces a conformational change to the DNA sequences leading us to hypothesize that PICH regulates transcription by remodeling DNA. PICH ablation leads to reduced expression of Nrf2 and impaired antioxidant response leading to increased ROS content, thus, showing PICH is essential for the cell to respond to oxidative stress.


2016 ◽  
Vol 180 ◽  
pp. 141-154 ◽  
Author(s):  
Larissa M. Williams ◽  
Briony A. Lago ◽  
Andrew G. McArthur ◽  
Amogelang R. Raphenya ◽  
Nicholas Pray ◽  
...  

Plant Science ◽  
2020 ◽  
Vol 301 ◽  
pp. 110689
Author(s):  
Xing-Long Ji ◽  
Hong-Liang Li ◽  
Zhi-Wen Qiao ◽  
Jiu-Cheng Zhang ◽  
Wei-Jian Sun ◽  
...  

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