Genetic Variants in the STMN1 Transcriptional Regulatory Region Affect Promoter Activity and Fear Behavior in English Springer Spaniels

Xiao-lin, Ding; Hu, Jin; Zhang, Hanying; Xu, Yinxue

doi:10.1371/journal.pone.0158756

Cited by 5 publications

(6 citation statements)

References 56 publications

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“…We transiently transfected primary granulosa cells with these constructs as well as a control vector bearing no promoter (pGL3-Basic), and measured the luciferase activity. 0.5k-Luc showed significantly higher activity than 6.1k-Luc ( Figure 5A), which was consistent with previous studies reporting that a shorter sequence often possessed higher promoter activity in transient assay (56)(57)(58)(59).…”

Section: Lncrna-amhr2 Activation Increases Amhr2 Promoter Activity Insupporting

confidence: 92%

A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells

et al. 2017

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Anti-Müllerian hormone (AMH) is critical to the regression of Müllerian ducts during mammalian male differentiation and targets ovarian granulosa cells and testicular Sertoli and Leydig cells of adults. Specific effects of AMH are exerted via its receptor, AMH type II receptor (Amhr2), but the mechanism by which the Amhr2 gene is specifically activated is not fully understood. To see whether a proximal promoter was sufficient for Amhr2 gene activation, we generated transgenic mice that bore the enhanced green fluorescent protein (EGFP) gene driven by a 500-bp mouse Amhr2 gene promoter. None of the established 10 lines, however, showed appropriate EGFP expression, indicating that the 500-bp promoter was insufficient for Amhr2 gene activation. As a regulatory element, we found a long noncoding RNA, lncRNA-Amhr2, transcribed from upstream of the Amhr2 gene in ovarian granulosa cells and testicular Sertoli cells. In primary granulosa cells, knockdown of lncRNA-Amhr2 resulted in a decrease of Amhr2 messnger RNA level, and a transient reporter gene assay showed that lncRNA-Amhr2 activation increased Amhr2 promoter activity. The activity was correlated with lncRNA-Amhr2 transcription in stably transfected OV3121 cells derived from mouse granulosa cells. Moreover, by the Tet-on system, the induction of lncRNA-Amhr2 transcription dramatically increased Amhr2 promoter activity in OV3121 cells. These results indicate that lncRNA-Amhr2 plays a role in Amhr2 gene activation in ovarian granulosa cells by enhancing promoter activity, providing insight into Amhr2 gene regulation underlying the AMH signaling in the female reproductive system.

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Section: Lncrna-amhr2 Activation Increases Amhr2 Promoter Activity Insupporting

confidence: 92%

A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells

et al. 2017

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“…Some animal experiments have demonstrated that Stmin1 is involved in fear processing in mice 10 , 13 , 15 and dogs. 16 However, the number of experimental studies on the association of the Stmn1 gene with anxiety and fear in humans is limited. In 2010, Broke et al 18 used the acoustic startle paradigm and a standardized laboratory protocol for the induction of fear and psychosocial stress in 113 healthy German volunteers to investigate the impact of Stmn1 gene polymorphisms (rs182455 and rs213641) on 2 fear- and anxiety-controlling effector-systems of the amygdala and found that Stmn1 genotype interacting with individuals’ gender significantly impacts fear and anxiety responses and cortisol stress response.…”

Section: Discussionmentioning

confidence: 99%

“…Second, a number of studies have demonstrated that Stmn1 is involved in fear processing in experimental animals. 10 , 13 , 15 , 16 For example, by constructing a single prolonged stress rat model of post-traumatic stress disorder (PTSD), Shan et al 10 found that Stmn1 in the memory loop, especially in the hippocampus, regulates MT structure through its phosphorylation at Ser25 and Ser38 and thereby participates in the mediation of fear memory abnormalities in PTSD. Using Stmn1 knockout (KO) mice, many studies have demonstrated that Stmn1 KO could lead to abnormal spike-timing-dependent long-term potentiation (LTP) and defective memory on fear conditioning.…”

Section: Introductionmentioning

confidence: 99%

“… 13 , 15 , 17 These results indicate that Stmn1 is required for the induction of LTP in afferent inputs to the amygdala and is essential in regulating both innate and learned fear in mice. Using Stmn1 KO dogs, Ding et al 16 demonstrated that 2 SNPs, −327A > G and −125C > T, located in the Stmn1 gene promoter region could affect canine fear behavior by altering Stmn1 transcriptional activity.…”

Section: Introductionmentioning

confidence: 99%

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No Association of Stathmin 1 Gene Polymorphism with Trait or State Anxiety in the Chinese Population

Cong,

Zhang,

et al. 2024

ALPHA PSYCHIATRY

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Objective: Stathmin 1 (Stmn1) is a neuronal growth-associated protein which was found to be involved in fear processing both in animals and humans. Moreover, it has been demonstrated that 2 single nucleotide polymorphisms (SNPs) of the Stmn1 gene (rs182455 and rs213641) significantly impacted individual fear and anxiety responses in German. However, there have been no reports on the correlation between Stmn1 SNPs and anxiety in Chinese. The present study thus aimed to explore such correlation. Methods: A sample of 567 healthy Han Chinese adults were genotyped for the Stmn1 SNP, namely rs182455, using polymerase chain reaction and restriction fragment length polymorphism analysis. Anxiety was assessed by the Chinese version of 40-item State-Trait Anxiety Inventory (STAI), which measures 2 anxiety dimensions, state and trait anxiety. Results: The numbers of CC, CT, and TT genotypes of rs182455 polymorphism were 227 (40.0%), 263 (46.4%), and 77 (13.6%), respectively. The genotype distribution did not deviate from the Hardy–Weinberg equilibrium ( χ 2 = 0.004, P = .953). There were no significant differences in either state or trait anxiety among the 3 rs182455 genotype groups ( F = 0.457, 0.415, P = .634, .660), between the 2 dominant model groups ( t = 0.865, −0.195, P = .388, .845), or between the 2 recessive model groups ( t = 0.106, 0.906, P = .916, .365). Moreover, no significant gender-specific differences in any STAI scores were found among the rs182455 genotype groups (all P > .05). Conclusion: No evidence was demonstrated for the association of the Stmn1 gene polymorphism rs182455 with either trait or state anxiety in Chinese adults.

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“…Several studies have verified that stathmin1 transcription was regulated by wild type and mutant p53 [ 23 , 24 ]. Two SNPs identified in the canine stathmin1 promoter region could affect transcription factor binding [ 25 ]. MiR-34a downregulates stathmin1 by directly binding to its 3’-UTR [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Acetylation stabilizes stathmin1 and promotes its activity contributing to gallbladder cancer metastasis

Fan

Shen

et al. 2022

Cell Death Discov.

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Gallbladder cancer is the most common biliary tract malignant tumor with highly metastatic characters and poor prognosis. However, the underlying mechanism remains unclear. Stathmin1 is ubiquitous phosphoprotein, regulating microtubule stabilization. We identified the acetylation of stahtmin1 at lysine 9 (K9) in gallbladder cancer. K9 acetylation of stathmin1 was reversely regulated by the acetyltransferase PCAF and the deacetylases sirt2. K9 acetylation of stathmin1 inhibited the combining of stathmin1 to E3 ubiquitin ligase RLIM, thereby inhibiting its ubiquitination degradation. Moreover, K9 acetylation also promoted the activity of stahtmin1 interacting and destabilizing microtubule through the inhibition of stathmin1 phosphorylation. K9 acetylated stathmin1 significantly promoted gallbladder cancer cell migration and invasion viability in vitro and lung metastasis in vivo, and indicated poor prognosis of nude mice. IHC assay suggested the positive correlation of high levels of K9 acetylation and stathmin1 expression in gallbladder cancer. Our study revealed that K9 acetylation up-regulated stathmin1 protein stability and microtubule-destabilizing activity to promoted gallbladder cancer metastasis, which provides a potential target for gallbladder cancer therapy.

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Genetic Variants in the STMN1 Transcriptional Regulatory Region Affect Promoter Activity and Fear Behavior in English Springer Spaniels

Cited by 5 publications

References 56 publications

A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells

A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells

No Association of Stathmin 1 Gene Polymorphism with Trait or State Anxiety in the Chinese Population

Acetylation stabilizes stathmin1 and promotes its activity contributing to gallbladder cancer metastasis

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