Identification of tetratricopeptide repeat domain 9, a hormonally regulated protein

Cao, Shenglan; Iyer, Jayasree K.; Lin, Valerie Chun Ling

doi:10.1016/j.bbrc.2006.04.091

Cited by 23 publications

(26 citation statements)

References 15 publications

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“…Importantly, TTC9A and B are highly conserved and share all regulatory protein domains (Shrestha et al, 2015), suggesting that they may have functional similarities such that TTC9B may contribute to the sensitivity of estrogen signaling implicated in PPD. An important possibility requiring further study is that these loci may be involved in feedback inhibition, as another study suggested that TTC9A appeared to be a target of the ERα in mammary tissue (Shrestha et al, 2012) and previous research out of our laboratory and others implicates that in vitro and in vivo estradiol treatment alters TTC9B expression (Cao et al, 2006) and methylation (Guintivano et al, 2013a), respectively.…”

Section: Discussionmentioning

confidence: 96%

“…Both genes have ties to estrogen signaling. TTC9B expression has been shown to be responsive to gonadal hormones (Cao et al, 2006) and is discussed in depth below. HP1BP3 associates with ERβ in culture (Nassa et al, 2011), binds to chromatin specifically at the repressive histone 3 lysine 9 trimethylation (H3K9me3) mark, and is expressed in most tissues with 10-fold higher levels in the brain (Garfinkel et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels

Osborne

Clive

Kimmel

et al. 2015

Neuropsychopharmacol

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DNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood. The objective of this study was to replicate the predictive efficacy of the previously established model in women with and without a previous psychiatric diagnosis and to understand the effects of changing hormone levels on PPD biomarker loci. Using a statistical model trained on DNA methylation data from N = 51 high-risk women, we prospectively predicted PPD status in an independent N = 51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B, with an area under the receiver operator characteristic curve (AUC) of 0.81 (95% CI: 0.69-0.92, po5 × 10 − 4 ). Modeling DNA methylation of these genes in N = 240 women without a previous psychiatric diagnosis resulted in a cross-sectional prediction of PPD status with an AUC of 0.81 (95% CI: 0.68-0.93, p = 0.01). TTC9B and HP1BP3 DNA methylation at early antenatal time points showed moderate evidence for association to the change in estradiol and allopregnanolone over the course of pregnancy, suggesting that epigenetic variation at these loci may be important for mediating hormonal sensitivity. In addition both loci showed PPD-specific trajectories with age, possibly mediated by age-associated hormonal changes. The data add to the growing body of evidence suggesting that PPD is mediated by differential gene expression and epigenetic sensitivity to pregnancy hormones and that modeling proxies of this sensitivity enable accurate prediction of PPD.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels

Osborne

Clive

Kimmel

et al. 2015

Neuropsychopharmacol

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“…could regulate the expression of PR target genes in MDA-MB-231 cells. The genes tested were tetratricopeptide repeat domain 9 (TTC9) and IL8 which are known to be regulated by progesterone in PR-transfected MDA-MB-231 cells [23,24]. Figure 2a shows that in parental MDA-MB-231 cells and Ad/U-infected cell, progesterone had no effect on the expression of TTC9 and IL-8.…”

Section: Adenoviruses-mediated Pr Expression In Mcf-7 Cellsmentioning

confidence: 97%

Anti-estrogenic mechanism of unliganded progesterone receptor isoform B in breast cancer cells

Zheng

Bay

et al. 2007

Breast Cancer Res Treat

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Over half of breast cancer cases are estrogen-dependent and strategies to combat estrogen-dependent breast cancer have been to either block the activation of estrogen receptor (ER) or diminish the supply of estrogens. Our previous work documented that estrogen-independent expression of progesterone receptor (PR) in MCF-7 cells markedly disrupted the effects of estrogen. In this study, we have developed an adenovirus-mediated gene delivery system to study the specific involvement of PR isoform A (PR-A) and PR-B in the anti-estrogenic effect and its mechanism of action. The results revealed that PR-B, but not PR-A, exhibited distinct anti-estrogenic effect on E2-induced cell growth, gene expression, and ER-ERE interaction in a ligand-independent manner. The anti-estrogenic effect of PR-B was also associated with heightened metabolism and increased cellular uptake of estradiol-17 beta (E2). We have also found that the B-upstream segment of PR-B alone was able to inhibit E2-induced ER-ERE interaction and cellular uptake of E2. Although PR-A alone did not affect E2-induced ER activity, it antagonized the anti-estrogenic effect of PR-B in a concentration-dependent manner. The findings suggest an important mechanism of maintaining a favorable level of ER activity by PR-A and PR-B in estrogen target cells for optimal growth and differentiation. The potential anti-estrogenic mechanism of PR-B may be exploited for breast cancer therapy.

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“…1). TTC9A protein is ubiquitously expressed in all tissues after birth, with the highest expression in the brain and the lowest expression in the liver1516. TTC9A expression is regulated by both estrogen and progesterone in breast cancer cells.…”

mentioning

confidence: 99%

Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice

Lim

Shrestha

et al. 2016

Sci Rep

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Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A−/−) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A−/− mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A−/− mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A+/+ mice. This difference was abolished after ovariectomy, and administration of 17-β-estradiol benzoate (EB) restored this escalated anxiety-like behavior in TTC9A−/− mice. Since serotonin is well-known to be the key neuromodulator involved in anxiety behaviors, the mRNA levels of tryptophan hydroxylase (TPH) 1, TPH2 (both are involved in serotonin synthesis), and serotonin transporter (5-HTT) were measured in the ventromedial prefrontal cortex (vmPFC) and dorsal raphe nucleus (DRN). Interestingly, the heightened anxiety in TTC9A−/− mice under EB influence is consistent with a greater induction of TPH 2, and 5-HTT by EB in DRN that play key roles in emotion regulation. In conclusion, our data indicate that TTC9A modulates the anxiety-related behaviors through modulation of estrogen action on the serotonergic system in the DRN.

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Identification of tetratricopeptide repeat domain 9, a hormonally regulated protein

Cited by 23 publications

References 15 publications

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels

Anti-estrogenic mechanism of unliganded progesterone receptor isoform B in breast cancer cells

Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice

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