Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b

Science ◽  
2020 ◽  
Vol 368 (6488) ◽  
pp. 303-306 ◽  
Author(s):  
Ceri Weber ◽  
Yingjie Zhou ◽  
Jong Gwan Lee ◽  
Loren L. Looger ◽  
Guoying Qian ◽  
...  

In many reptiles, including the red-eared slider turtle Trachemys scripta elegans (T. scripta), sex is determined by ambient temperature during embryogenesis. We previously showed that the epigenetic regulator Kdm6b is elevated at the male-producing temperature and essential to activate the male pathway. In this work, we established a causal link between temperature and transcriptional regulation of Kdm6b. We show that signal transducer and activator of transcription 3 (STAT3) is phosphorylated at the warmer, female-producing temperature, binds the Kdm6b locus, and represses Kdm6b transcription, blocking the male pathway. Influx of Ca2+, a mediator of STAT3 phosphorylation, is elevated at the female temperature and acts as a temperature-sensitive regulator of STAT3 activation.

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Diana M. Morales-Prieto ◽  
Stephanie Ospina-Prieto ◽  
Wittaya Chaiwangyen ◽  
Maja Weber ◽  
Sebastian Hölters ◽  
...  

Invasiveness of trophoblast and choriocarcinoma cells is in part mediated via leukemia inhibitory factor- (LIF-) induced activation of signal transducer and activator of transcription 3 (STAT3). The regulation of STAT3 phosphorylation at its ser727 binding site, possible crosstalk with intracellular MAPK signaling, and their functional implications are the object of the present investigation. JEG-3 choriocarcinoma cells were cultured in presence/absence of LIF and the specific ERK1/2 inhibitor (U0126). Phosphorylation of signaling molecules (p-STAT3 (ser727 and tyr705) and p-ERK1/2 (thr 202/tyr 204)) was assessed per Western blot. Immunocytochemistry confirmed results, but also pinpointed the location of phosphorylated signaling molecules. STAT3 DNA-binding capacity was studied with a colorimetric ELISA-based assay. Cell viability and invasion capability were assessed by MTS and Matrigel assays. Our results demonstrate that LIF-induced phosphorylation of STAT3 (tyr705 and ser727) is significantly increased after blocking ERK1/2. STAT3 DNA-binding capacity and cell invasiveness are enhanced after LIF stimulation and ERK1/2 blockage. In contrast, proliferation is enhanced by LIF but reduced after ERK1/2 inhibition. The findings herein show that blocking ERK1/2 increases LIF-induced STAT3 phosphorylation and STAT3 DNA-binding capacity by an intranuclear crosstalk, which leads to enhanced invasiveness and reduced proliferation.


Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1509-1519 ◽  
Author(s):  
Marieke Ruiter ◽  
Patricia Duffy ◽  
Steven Simasko ◽  
Robert C. Ritter

Reduction of food intake and body weight by leptin is attributed largely to its action in the hypothalamus. However, the signaling splice variant of the leptin receptor, LRb, also is expressed in the hindbrain, and leptin injections into the fourth cerebral ventricle or dorsal vagal complex are associated with reductions of feeding and body weight comparable to those induced by forebrain leptin administration. Although these observations suggest direct hindbrain action of leptin on feeding and body weight, the possibility that hindbrain leptin administration also activates the Janus kinase/signal transducer and activator of transcription 3 (STAT3) signaling in the hypothalamus has not been investigated. Confirming earlier work, we found that leptin produced comparable reductions of feeding and body weight when injected into the lateral ventricle or the fourth ventricle. We also found that lateral and fourth ventricle leptin injections produced comparable increases of STAT3 phosphorylation in both the hindbrain and the hypothalamus. Moreover, injection of 50 ng of leptin directly into the nucleus of the solitary tract also increased STAT3 phosphorylation in the hypothalamic arcuate and ventromedial nuclei. Increased hypothalamic STAT3 phosphorylation was not due to elevation of blood leptin concentrations and the pattern of STAT3 phosphorylation did not overlap distribution of the retrograde tracer, fluorogold, injected via the same cannula. Our observations indicate that even small leptin doses administered to the hindbrain can trigger leptin-related signaling in the forebrain, and raise the possibility that STAT3 phosphorylation in the hypothalamus may contribute to behavioral and metabolic changes observed after hindbrain leptin injections.


2020 ◽  
Vol 12 (4) ◽  
pp. 456-462 ◽  
Author(s):  
Warren Brian Simison ◽  
James F Parham ◽  
Theodore J Papenfuss ◽  
Athena W Lam ◽  
James B Henderson

Abstract Among vertebrates, turtles have many unique characteristics providing biologists with opportunities to study novel evolutionary innovations and processes. We present here a high-quality, partially phased, and chromosome-level Red-Eared Slider (Trachemys scripta elegans, TSE) genome as a reference for future research on turtle and tetrapod evolution. This TSE assembly is 2.269 Gb in length, has one of the highest scaffold N50 and N90 values of any published turtle genome to date (N50 = 129.68 Mb and N90 = 19 Mb), and has a total of 28,415 annotated genes. We introduce synteny analyses using BUSCO single-copy orthologs, which reveal two chromosome fusion events accounting for differences in chromosome counts between emydids and other cryptodire turtles and reveal many fission/fusion events for birds, crocodiles, and snakes relative to TSE. This annotated chromosome-level genome will provide an important reference genome for future studies on turtle, vertebrate, and chromosome evolution.


2006 ◽  
Vol 159 (4) ◽  
pp. 122-123 ◽  
Author(s):  
J. Hidalgo-Vila ◽  
A. Martinez-Silvestre ◽  
C. Diaz-Paniagua

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