scholarly journals HNF4beta, a new gene of the HNF4 family with distinct activation and expression profiles in oogenesis and embryogenesis of Xenopus laevis.

1997 ◽  
Vol 17 (2) ◽  
pp. 687-694 ◽  
Author(s):  
B Holewa ◽  
D Zapp ◽  
T Drewes ◽  
S Senkel ◽  
G U Ryffel

The transcription factor hepatocyte nuclear factor 4 (HNF4) is an orphan member of the nuclear receptor superfamily expressed in mammals in liver, kidney, and the digestive tract. Recently, we isolated the Xenopus homolog of mammalian HNF4 and revealed that it is not only a tissue-specific transcription factor but also a maternal component of the Xenopus egg and distributed within an animal-to-vegetal gradient. We speculate that this gradient cooperates with the vegetally localized embryonic induction factor activin A to activate expression of HNF1alpha, a tissue-specific transcription factor with an expression pattern overlapping that of HNF4. We have now identified a second Xenopus HNF4 gene, which is more distantly related to mammalian HNF4 than the previously isolated gene. This new gene was named HNF4beta to distinguish it from the known HNF4 gene, which is now called HNF4alpha. By reverse transcription-PCR, we detected within the 5' untranslated region of HNF4beta two splice variants (HNF4beta2 and HNF4beta3) with additional exons, which seem to affect RNA stability. HNF4beta is a functional transcription factor acting sequence specifically on HNF4 binding sites known for HNF4alpha, but it seems to have a lower DNA binding activity and is a weaker transactivator than the alpha isoform. Furthermore, the two factors differ with respect to tissue distribution in adult frogs: whereas HNF4alpha is expressed in liver and kidney, HNF4beta is expressed in addition in stomach, intestine, lung, ovary, and testis. Both factors are maternal proteins and present at constant levels throughout embryogenesis. However, using reverse transcription-PCR, we found the RNA levels to change substantially: whereas HNF4alpha is expressed early during oogenesis and is absent in the egg, HNF4beta is first detected in the latest stage of oogenesis, and transcripts are present in the egg and early cleavage stages. Furthermore, zygotic HNF4alpha transcripts appear in early gastrula and accumulate during further embryogenesis, whereas HNF4beta mRNA transiently appears during gastrulation before it accumulates again at the tail bud stage. All of these distinct characteristics of the newly identified HNF4 protein imply that the alpha and beta isoform have different functions in development and in adult tissues.

Author(s):  
José-Luis Castrillo ◽  
Lars E. Theill ◽  
Mordechai Bodner ◽  
Michael Karin

2020 ◽  
Author(s):  
Tian Qi Zhang ◽  
Qingqiang Dai ◽  
Maneesh Kumarsing Beeharry ◽  
Zhenqiang Wang ◽  
Liping Su ◽  
...  

Abstract Background: Gastric Cancer (GC) is one of the leading causes of cancer-related deaths and mortality. Long non-coding RNAs (lncRNAs) such as SNHG12 play important roles in the pathogenesis and progression of cancers. However, the role and significanve of SNHG12 in the metastasis of GC has not yet been thoroughly investigated.Methods: The SNHG12 expression pattern was detected in GC tissue samples from our faculty and cell lines using quantitative reverse transcription PCR. In vivo and in vitro gain and loss assays were conducted to observe the effects of SNHG12 regulation on GC cell metastasis potential. The underlying mechanisms of SNHG12 regulation on EMT and metastatic potential of GC cells were further determined by quantitative reverse transcription PCR, western blotting, dual luciferase reporter assays, co-immunoprecipitation, immunoprecipitation, RIP assays, TOPFlash/FOPFlash reporter assays and Ch-IP assays.Results: SNHG12 was upregulated in GC tissues and cell lines. The expression levels of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM staging and lymph node metastasis, and was associated with poorer DFS and OS in the GC patients. SNHG12 was significantly highly expressed in peritoneal metastatic tissues from GC patients and mice subjects, suggesting a possible role of SNHG12 in peritoneal carcinomatosis from GC. Further in vivo and in vitro gain and loss assays indicated that SNHG12 promoted GC metastasis and EMT. Based on hypothetical bioinformatic analysis findings, our mechanistic analyses revealed that miR-218-5p was a direct target of SNHG12 and suggested that both SNHG12 and miR-218-5p could collectively regulate YWHAZ, forming the SNHG12/ miR-218-5p/YWHAZ axis, hereby decreasing the ubiquitination of β-catenin, thus activating the β-catenin signaling pathway and facilitating metastasis and EMT. Further analysis also revealed that the transcription factor YY1 could negatively modulate SNHG12 transcription.Conclusions: Our findings demonstrate that SNHG12 is be a potential prognostic marker and therapeutic target for GC. Negatively modulated by transcription factor YYI, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and hence activating the β-catenin signaling pathway. Furthermore, we discovered high SNHG12 expression could be related to peritoneal carcinomatosis from GC but this requires further validation.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Suzanne M. K. Buckley ◽  
Juliette M. K. M. Delhove ◽  
Dany P. Perocheau ◽  
Rajvinder Karda ◽  
Ahad A. Rahim ◽  
...  

1997 ◽  
Vol 266 (2) ◽  
pp. 231-245 ◽  
Author(s):  
François Tronche ◽  
François Ringeisen ◽  
Marta Blumenfeld ◽  
Moshe Yaniv ◽  
Marco Pontoglio

1993 ◽  
Vol 13 (10) ◽  
pp. 6416-6426 ◽  
Author(s):  
D Zapp ◽  
S Bartkowski ◽  
B Holewa ◽  
C Zoidl ◽  
L Klein-Hitpass ◽  
...  

LFB1 (HNF1) is a tissue-specific transcription factor found in the livers, stomachs, intestines, and kidneys of vertebrates. By analyzing the promoter of the Xenopus LFB1 gene, we identified potential autoregulation by LFB1 and regulation by HNF4, a transcription factor with a tissue distribution similar to that of LFB1. Injection of LFB1 promoter-chloramphenicol acetyltransferase constructs into Xenopus eggs revealed embryonic activation that is restricted to the region of the developing larvae expressing endogeneous LFB1. Proper embryonic activation was also observed with a rat LFB1 promoter. Deletion analysis of the Xenopus and rat promoters revealed that in both promoters embryonic activation is absolutely dependnet on the presence of an element that contains CCNCTCTC as the core consensus sequence. Since this element is recognized by the maternal factor OZ-1 previously described by N. Ovsenek, A. M. Zorn, and P. A. Krieg (Development 115:649-655, 1992), we might have identified the main constituents of a hierarchy that leads via LFB1 to the activation of tissue-specific genes during embryogenesis.


Biology Open ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. bio052928 ◽  
Author(s):  
Alicia Estacio-Gómez ◽  
Amira Hassan ◽  
Emma Walmsley ◽  
Lily Wong Le ◽  
Tony D. Southall

2009 ◽  
Vol 37 (19) ◽  
pp. 6305-6315 ◽  
Author(s):  
Helge G. Roider ◽  
Boris Lenhard ◽  
Aditi Kanhere ◽  
Stefan A. Haas ◽  
Martin Vingron

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