Newly identified interferon tau-responsive Hes family BHLH transcription factor 4 and cytidine/uridine monophosphate kinase 2 genes in peripheral blood granulocytes during early pregnancy in cows

2019 ◽  
Vol 68 ◽  
pp. 64-72
Author(s):  
M. Kikuchi ◽  
K. Kizaki ◽  
S. Shigeno ◽  
N. Toji ◽  
T. Ishiguro-Oonuma ◽  
...  
Development ◽  
2021 ◽  
Author(s):  
Marie-Theres Wittmann ◽  
Sayako Katada ◽  
Elisabeth Sock ◽  
Philipp Kirchner ◽  
Arif B. Ekici ◽  
...  

Transcription factor 4 (TCF4) is a critical regulator of neurodevelopment and has been linked to the pathogenesis of autism, intellectual disability, and schizophrenia. As a class I bHLH transcription factor it is assumed that TCF4 exerts its neurodevelopmental functions through dimerization with proneural class II bHLH TFs. Here, we aim to identify transcription factor (TF) partners of TCF4 in the control of interhemispheric connectivity formation. Using a new bioinformatic strategy integrating TF expression levels and regulon activities from single cell RNA-sequencing data, we find evidence that TCF4 interacts with non-bHLH TFs and modulates their transcriptional activity in Satb2+ intercortical projection neurons. Notably, this network comprises regulators linked to the pathogenesis of neurodevelopmental disorders, e.g. FOXG1, SOX11 and BRG1. In support of the functional interaction of TCF4 with non-bHLH TFs we find that TCF4 and SOX11 biochemically interact and cooperatively control commissure formation in vivo, and regulate the transcription of genes implied in this process. Next to identifying new candidate interactors of TCF4 in neurodevelopment, this study illustrates how scRNA-Seq data can be leveraged to predict TFs networks in neurodevelopmental processes.


2019 ◽  
Author(s):  
Laura Tamberg ◽  
Mariliis Jaago ◽  
Kristi Säälik ◽  
Anastassia Shubina ◽  
Carl Sander Kiir ◽  
...  

AbstractMammalian Transcription Factor 4 (TCF4) has been linked to schizophrenia and intellectual disabilities like Pitt-Hopkins syndrome (PTHS). Here we show that similarly to mammalian TCF4, fruit fly orthologue Daughterless (Da) is expressed in the Drosophila brain structures associated with learning and memory, the mushroom bodies. Furthermore, silencing of da in mushroom body neurons impairs appetitive associative learning of the larvae and leads to decreased levels of the synaptic proteins Synapsin (Syn) and discs large 1 (dlg1) suggesting the involvement of Da in memory formation. Here we demonstrate that Syn and dlg1 are direct target genes of Da in adult Drosophila heads, since Da binds to the regulatory regions of these genes and the modulation of Da levels alter the levels of Syn and dlg1 mRNA. Silencing of da also affects negative geotaxis of the adult flies suggesting the impairment of locomotor function. Overall, our findings suggest that Da regulates Drosophila larval memory and adult negative geotaxis possibly via its synaptic target genes Syn and dlg1. These behavioural phenotypes can be further used as a PTHS model to screen for therapeutics.Summary statementHuman TCF4, a bHLH transcription factor, is associated with intellectual disability and schizophrenia. Here we propose a Drosophila model for human disease studies using TCF4 orthologue in fruit fly, Daughterless.


Reproduction ◽  
2000 ◽  
pp. 387-395 ◽  
Author(s):  
KJ Demmers ◽  
HN Jabbour ◽  
DW Deakin ◽  
AP Flint

The role of interferon in early pregnancy in red deer was investigated by (a) measuring production of interferon by the conceptus, (b) testing the anti-luteolytic effect of recombinant interferon-tau in non-pregnant hinds, and (c) treatment of hinds with interferon after asynchronous embryo transfer. Blastocysts were collected from 34 hinds by uterine flushing 14 (n = 2), 16 (n = 2), 18 (n = 8), 20 (n = 13) or 22 (n = 9) days after synchronization of oestrus with progesterone withdrawal. Interferon anti-viral activity was detectable in uterine flushings from day 16 to day 22, and increased with duration of gestation (P < 0.01) and developmental stage (P < 0.01). When interferon-tau was administered daily between day 14 and day 20 to non-pregnant hinds to mimic natural blastocyst production, luteolysis was delayed by a dose of 0.2 mg day(-1) (27.3 +/- 1.3 days after synchronization, n = 4 versus 21 +/- 0 days in control hinds, n = 3; P < 0.05). Interferon-tau was administered to hinds after asynchronous embryo transfer to determine whether it protects the conceptus against early pregnancy loss. Embryos (n = 24) collected on day 6 from naturally mated, superovulated donors (n = 15) were transferred into synchronized recipients on day 10 or day 11. Interferon-tau treatment (0.2 mg daily from day 14 to 20) increased calving rate from 0 to 64% in all recipients (0/11 versus 7/11, P < 0.005), and from 0 to 67% in day 10 recipients (0/8 versus 6/9, P < 0.01). The increased success rate of asynchronous embryo transfer after interferon-tau treatment in cervids may be of benefit where mismatched embryo-maternal signalling leads to failure in the establishment of pregnancy.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kaijie Zheng ◽  
Xutong Wang ◽  
Yating Wang ◽  
Shucai Wang

Abstract Background Trichome initiation in Arabidopsis is regulated by a MYB-bHLH-WD40 (MBW) transcriptional activator complex formed by the R2R3 MYB transcription factor GLABRA1 (GL1), MYB23 or MYB82, the bHLH transcription factor GLABRA3 (GL3), ENHANCER OF GLABRA3 (EGL3) or TRANSPARENT TESTA8 (TT8), and the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). However, the functions of the rice homologs of the MBW complex proteins remained uncharacterized. Results Based on amino acid sequence identity and similarity, and protein interaction prediction, we identified OsGL1s, OsGL3s and OsTTG1s as rice homologs of the MBW complex proteins. By using protoplast transfection, we show that OsGL1D, OsGL1E, OsGL3B and OsTTG1A were predominantly localized in the nucleus, OsGL3B functions as a transcriptional activator and is able to interact with GL1 and TTG1. By using yeast two-hybrid and protoplast transfection assays, we show that OsGL3B is able to interact with OsGL1E and OsTTG1A, and OsGL1E and OsTTG1A are also able to interact with GL3. On the other hand, we found that OsGL1D functions as a transcription activator, and it can interact with GL3 but not OsGL3B. Furthermore, our results show that expression of OsTTG1A in the ttg1 mutant restored the phenotypes including alternations in trichome and root hair formation, seed color, mucilage production and anthocyanin biosynthesis, indicating that OsTTG1A and TTG1 may have similar functions. Conclusion These results suggest that the rice homologs of the Arabidopsis MBW complex proteins are able to form MBW complexes, but may have conserved and non-conserved functions.


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