Transcription Factor
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2022 ◽  
Vol 293 ◽  
pp. 110674
Author(s):  
Yiguang Wang ◽  
Li-Jie Zhou ◽  
Yuxi Wang ◽  
Zhiqiang Geng ◽  
Baoqing Ding ◽  
...  

Author(s):  
Chunying Zhang ◽  
Lin Yang ◽  
Ge Zhao ◽  
Jiaxiang Wang ◽  
Juntao Pan ◽  
...  

Neuroblastoma (NBL) exists as the most common solid malignancy which predominantly occurs in children. Long non-coding RNAs (lncRNAs) have been widely confirmed to exert functions in modulating the pathogenesis of diverse diseases. Nevertheless, whether the putative function of long intergenic non-protein coding RNA 1518 (LINC01518) in NBL has not been elucidated yet. In this study, RT-qPCR was used for determining LINC01518 expression and LINC01518 was found to be notably overexpressed in NBL tissues and cell lines compared with normal nerve tissues and cell lines. Functional experiments and mechanism assays were respectively done for the investigation into cell phenotype and for the exploration of correlation among genes. LINC01518 silencing was discovered to repress cell malignant phenotype. We observed that GATA binding protein 3 (GATA3) was an active transcription factor of LINC01518. Besides, LINC01518 functioned as a competing endogenous RNA (ceRNA), which sequestered microRNA-206 (miR-206) to up-regulate protein kinase cAMP-activated catalytic subunit beta (PRKACB). Afterwards, rescue assays validated the oncogenic role of GATA3/LINC01518/miR-206/PRKACB axis in NBL. To be summarized, our research determined that LINC01518 might be used as a putative molecular marker for NBL diagnosis and treatment.


2021 ◽  
Vol 6 ◽  
pp. 290
Author(s):  
Alexander T. Williams ◽  
Nick Shrine ◽  
Hardeep Naghra-van Gijzel ◽  
Joanna C. Betts ◽  
Edith M. Hessel ◽  
...  

Background: Globally, respiratory infections contribute to significant morbidity and mortality. However, genetic determinants of respiratory infections are understudied and remain poorly understood. Methods: We conducted a genome-wide association study in 19,459 hospitalised respiratory infection cases and 101,438 controls from UK Biobank. We followed-up well-imputed top signals from the UK Biobank discovery analysis in 50,912 respiratory infection cases and 150,442 controls from 11 cohorts. We aggregated effect estimates across studies using inverse variance-weighted meta-analyses. Additionally, we investigated the function of the top signals in order to gain understanding of the underlying biological mechanisms. Results: In the discovery analysis, we report 56 signals at P<5×10-6, one of which was genome-wide significant (P<5×10-8). The genome-wide significant signal was in an intron of PBX3, a gene that encodes pre-B-cell leukaemia transcription factor 3, a homeodomain-containing transcription factor. Further, the genome-wide significant signal was found to colocalise with gene-specific expression quantitative trait loci (eQTLs) affecting expression of PBX3 in lung tissue, where the respiratory infection risk alleles were associated with decreased PBX3 expression in lung tissue, highlighting a possible biological mechanism. Of the 56 signals, 40 were well-imputed in UK Biobank and were investigated in the 11 follow-up cohorts. None of the 40 signals replicated, with effect estimates attenuated. Conclusions: Our discovery analysis implicated PBX3 as a candidate causal gene and suggests a possible role of transcription factor binding activity in respiratory infection susceptibility. However, the PBX3 signal, and the other well-imputed signals, did not replicate when aggregating effect estimates across 11 independent cohorts. Significant phenotypic heterogeneity and differences in study ascertainment may have contributed to this lack of statistical replication. Overall, our study highlighted putative associations and possible biological mechanisms that may provide insight into respiratory infection susceptibility.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mathieu Mancini ◽  
Benoît Charbonneau ◽  
David Langlais ◽  
Silvia M. Vidal

AbstractHerpes simplex virus type 1 (HSV-1) is the predominant cause of herpes simplex encephalitis (HSE), a condition characterized by acute inflammation and viral replication in the brain. Host genetics contribute to HSE onset, including monogenic defects in type I interferon signaling in cases of childhood HSE. Mouse models suggest a further contribution of immune cell-mediated inflammation to HSE pathogenesis. We have previously described a truncating mutation in the c-Rel transcription factor (RelC307X) that drives lethal HSE in 60% of HSV-1-infected RelC307X mice. In this study, we combined dual host-virus RNA sequencing with flow cytometry to explore cell populations and mechanisms involved in RelC307X-driven HSE. At day 5 postinfection, prior to HSE clinical symptom onset, elevated HSV-1 transcription was detected together with augmented host interferon-stimulated and inflammatory gene expression in the brainstems of high-responding RelC307X mice, predictive of HSE development. This early induction of host gene expression preceded pathological infiltration of myeloid and T cells in RelC307X mice at HSE onset by day 7. Thus, we establish c-Rel as an early regulator of viral and host responses during mouse HSE. These data further highlight the importance of achieving a balanced immune response and avoiding excess interferon-driven inflammation to promote HSE resistance.


2021 ◽  
Author(s):  
James S Chavez ◽  
Jennifer L Rabe ◽  
Giovanny Hernandez ◽  
Taylor S Mills ◽  
Katia E Nino ◽  
...  

The transcription factor PU.1 is a critical regulator of lineage fate in blood-forming hematopoietic stem cells (HSC). In response to inflammatory signals, PU.1 expression is increased in HSC, activating myeloid differentiation genes while repressing cell cycle and protein synthesis genes. To address potential functional heterogeneity arising in the phenotypic HSC compartment due to changes in PU.1 expression, here we fractionated phenotypic HSC using the SLAM code in conjunction with PU.1 expression levels using the PU.1-EYFP reporter mouse strain. While PU.1lo SLAM cells contain extensive long-term repopulating activity and a molecular signature corresponding to HSC activity at steady state, under inflammatory conditions the PU.1lo SLAM fraction is comprised almost entirely of HSC-like cells containing extensive short-term megakaryocytic potential. Our data demonstrate that the phenotypic HSC gate is heterogenous, and that similar PU.1 transcription factor levels can be tied to distinct functional activities under steady-state and inflammatory conditions.


2021 ◽  
Author(s):  
Yanze Song ◽  
Min Chen ◽  
Min Chen ◽  
Haoyi Wang ◽  
Fei Gao ◽  
...  

Sry on the Y chromosome is the master switch in sex determination in mammals. It has been well established that Sry encodes a transcription factor that is transiently expressed in somatic cells of male gonad, inducing a series of events that lead to the formation of testes. In the testis of adult mice, Sry is expressed as a circular RNA (circRNA) transcript, a type of noncoding RNA that forms a covalently linked continuous loop. However, the physiological function of this Sry circRNA (circSry) remains unknown since its discovery in 1993. Here we show that circSry is mainly expressed in the spermatocytes, but not in mature sperms and Sertoli cells. Loss of circSry led to the reduction of sperm number and the defect of germ cell development. The expression of γH2AX was decreased and failure of XY body formation was noted in circSry KO germ cells. Further study demonstrates that circSry regulates H2AX mRNA indirectly in pachytene spermatocytes through sponging miR-138-5p. Our study demonstrates that, in addition to its well-known sex-determination function, Sry also plays important role in spermatogenesis as a circRNA.


Author(s):  
Md. Qamrul Islam ◽  
Md. Nazmul Hasan ◽  
Hammadul Hoque ◽  
Nurnabi Azad Jewel ◽  
Md. Fahmid Hossain Bhuiyan ◽  
...  

Abstract Background Nitrogen and potassium are crucial supplements for plant development and growth. Plants can detect potassium and nitrate ions in soils and in like way, they modify root-to-shoot transport of these ions to adjust the conveyance among roots and shoots. Transcription factor MYB59 plays essential roles in numerous physiological processes inclusive of hormone response, abiotic stress tolerance, plant development, and metabolic regulation. In this study, we retrieved 56 MYB59 proteins from different plant species. Multiple sequence alignment, phylogenetic tree, conserved motif, chromosomal localization, and cis-regulatory elements of the retrieved sequences were analyzed. Gene structure, protein 3D structure, and DNA binding of OsMYB59 indica were also predicted. Finally, we characterized OsMYB59 and its function under low K+/NO3− conditions in Oryza sativa subsp. indica. Results Data analysis showed that MYB59s from various groups separated in terms of conserved functional domains and gene structure, where members of genus Oryza clustered together. Plants showed reduced height and yellowish appearance when grown on K+ and NO3− deficient medium. Quantitative real-time PCR uncovered that the OsMYB59 reacted to abiotic stresses where its expression was increased in BRRI dhan56 but decreased in other varieties on K+ deficient medium. In addition, OsMYB59 transcript level increased on NO3− deficient medium. Conclusions Our results can help to explain the biological functions of indica rice MYB59 protein and gave a theoretical premise to additionally describe its biological roles in response to abiotic stresses particularly drought.


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