BHLH transcription factor ATOH8 overexpression effect on endothelial cells: gain-of-function model [GOF]
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PROVIDER: PRJNA413501 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of human umbilical vein endothelial cells (HUVECs) adenovirally expressing the transcription factor ATOH8.
2019-10-17 | GSE104683 | GEO
Project description:The basic helix-loop-helix (bHLH) transcription factor ‘Atoh8’ is involved in the regulaton of several developmental processes and pathologies. It regulates organogenesis, reprogramming, stem cell fate determination, and cancer development. However, the mech anisms underlying these observations remain unclear. Unlike many tissue-specific bHLH factors, Atoh8 is ubiquitously expressed during development as well as in adult tissue. In this study, we explored whether Atoh8 modulates basic cellular functions, which may reveal a common mechanism that could explain the diverse observations reported in the literature. In the present study, our findings indicate that the loss of Atoh8 impairs autophagy. We observed differential expression of LC3B-II, TFEB, and accumulation of p62 in the absence or downregulation of Atoh8 in multiple cell lines. Moreover, mass spectrometric analysis of protein lysates from the tibialis anterior (TA) muscle in both wildtype and Atoh8 knockout mice revealed a significant downregulation of proteins associated with the initiation of autophagy (DEPTOR, PRAS40), autophagosome maturation (PDCD6IP, CHMP5), and autolysosomal degradation (NPC2, CTSB, CTSL). Additionally, the analysis indicated altered metabolism in the absence of Atoh8. Moreover, we determined that persistently elevated levels of reactive oxygen species (ROS) may be the primary factor contributing to the impairment of autophagy in the absence or downregulation of Atoh8.Overall, this study underscores that Atoh8 is a crucial regulator of autophagy, and its reduction or absence disrupts the autophagic process.
2026-01-05 | PXD070896 | Pride
Project description:Atoh8 is a transcription factor of the basic-helix-loop-helix (bHLH) family that is expressed in multiple tissues during embryonic development but whose specific functions remain unknown. The gene encoding Atoh8 is induced by various lineage- determining bHLH transcription factors in cell culture, suggesting a possible common role of this gene in multiple bHLH-driven differentiation programs. In the pancreas, the pro-endocrine bHLH factors Neurogenin3 (Neurog3) and NeuroD1 activate Atoh8 expression. Moreover, Atoh8 is expressed in the embryonic pancreas confirming its participation in the pancreatic transcriptional cascade. This work aims at gaining insight into the molecular function of Atoh8 during the endocrine differentiation program initiated by Neurog3 in the pancreas. To this aim, we have generated a recombinant adenovirus encoding an Atoh8-specific shRNA (Ad-shAtoh8) and used it to down-regulate expression of the Atoh8 gene in Neurog3-expressing pancreatic ductal cells (mPAC), a cellular model of endocrine cell differentiation. Thus, we have compared global changes in gene expression profiles between cells treated with Ad-Neurog3+shControl and cells treated with Ad-Neurog3+shAtoh8 using Affymetrix microarrays. Our results show that Atoh8 silencing significantly affects the expression of 293 genes in Neurog3-expressing mPAC cells. Gene Ontology analysis has revealed cell cycle as the biological function most significantly represented among the modified genes. These results uncover a potential function of Math6 as a regulator of cell cycle progression and provide novel insights into the link between Neurog3 and the regulation of the cell cycle. mPAC cells (mouse pancreatic duct cells) overexpressing Neurogenin3 were divided in 2 groups according to the shRNA encoded by the recombinant adenoviruses used: 1) Scramble shRNA (control for the infection effect), 2) Atonal Homolog 8-specific shRNA. Experiment was performed three independent times (3 independent biological replicates).
2014-10-10 | E-GEOD-43536 | biostudies-arrayexpress
Project description:Extravillous trophoblasts (EVTs) play a vital role in placental development by anchoring the placenta to the uterine wall, invading the maternal decidua, and remodeling maternal spiral arteries. ATOH8, a basic helix-loop-helix (bHLH) transcription factor, is central to regulating trophoblast dynamics at the maternal-fetal interface, where it orchestrates their invasive potential, proliferative capacity, and differentiation in mice. By coordinating these processes, ATOH8 ensures the formation of a functional placental structure critical for sustaining pregnancy. Although ATOH8 has been implicated in decidualization—a key preparatory event in human endometrial stromal fibroblasts essential for placental development, its precise mechanisms and contributions to human trophoblast function remain unresolved. To understand the role of ATOH8 in EVT differentiation, we performed RNA sequencing of ATOH8-depleted EVT and control EVT.
2025-12-04 | GSE293496 | GEO
Project description:Atoh8 is a transcription factor of the basic-helix-loop-helix (bHLH) family that is expressed in multiple tissues during embryonic development but whose specific functions remain unknown. The gene encoding Atoh8 is induced by various lineage- determining bHLH transcription factors in cell culture, suggesting a possible common role of this gene in multiple bHLH-driven differentiation programs. In the pancreas, the pro-endocrine bHLH factors Neurogenin3 (Neurog3) and NeuroD1 activate Atoh8 expression. Moreover, Atoh8 is expressed in the embryonic pancreas confirming its participation in the pancreatic transcriptional cascade. This work aims at gaining insight into the molecular function of Atoh8 during the endocrine differentiation program initiated by Neurog3 in the pancreas. To this aim, we have generated a recombinant adenovirus encoding an Atoh8-specific shRNA (Ad-shAtoh8) and used it to down-regulate expression of the Atoh8 gene in Neurog3-expressing pancreatic ductal cells (mPAC), a cellular model of endocrine cell differentiation. Thus, we have compared global changes in gene expression profiles between cells treated with Ad-Neurog3+shControl and cells treated with Ad-Neurog3+shAtoh8 using Affymetrix microarrays. Our results show that Atoh8 silencing significantly affects the expression of 293 genes in Neurog3-expressing mPAC cells. Gene Ontology analysis has revealed cell cycle as the biological function most significantly represented among the modified genes. These results uncover a potential function of Math6 as a regulator of cell cycle progression and provide novel insights into the link between Neurog3 and the regulation of the cell cycle.
2019-01-05 | GSE43537 | GEO
Project description:Analysis of human umbilical vein endothelial cells (HUVECs) depleted for the transcription factor ATOH8.
2019-10-17 | GSE104684 | GEO
Project description:bHLH transcription factor ATOH8 depletion effect on endothelial cells: loss-of-function model [LOF]
| PRJNA413502 | ENA
Project description:The basic helix-loop-helix (bHLH) transcription factors of the Drosophila’s atonal-related superfamily Neurogenin3 (Neurog3) and NeuroD1 promote endocrine differentiation in the gastrointestinal tract. Atonal Homolog 8 (Atoh8/Math6) is a newly identified member of the atonal-related family whose expression is induced by Neurog3 and NeuroD1 in cell culture, indicating a possible role for this gene in the endocrine differentiation program downstream of these two pro-endocrine factors. Intriguingly, available experimental evidence based on a reduced number of genes suggests that Atoh8 may negatively regulate Neurog3-targeting events. In this study, we have analyzed global changes in gene expression profiles upon exogenous expression of Atoh8 alone or in combination with Neurog3 in mouse pancreatic duct (mPAC) cells. These cells activate neuroendocrine-specific gene expression in response to Neurog3 and NeuroD1 and thus serve as an optimal model to evaluate the proendocrine activity of Atoh8. We have compared transcriptional profiles between mPAC cells treated with a recombinant adenovirus expressing Atoh8 (Ad-Atoh8) or a control adenovirus encoding B-galactosidase (Ad-Bgal), and between cells treated with Ad-Neurog3+Ad-Bgal or cells treated with Ad-Neurog3+Ad-Atoh8. The results obtained show that Atoh8 exhibits a very modest transcriptional activity in these cells thus confirming that Atoh8 does not function as a proendocrine gene. Furthermore, our data also confirm the ability of Atoh8 to block Neurog3-dependent transcriptional activation events. However, since repression is only seen for a small subset of Neurog3 gene targets, we discard a general role of Atoh8 as a negative regulator of Neurog3 pro-endocrine activity.
2014-10-10 | GSE43536 | GEO
Project description:Ferroptosis, a non-apoptotic programmed cell death triggered by excessive iron-dependent lipid peroxidation, plays a pivotal role in tumor progression. Significant progress has been made in elucidating the role of transcription factors in the regulation of ferroptosis. Nevertheless, the identification of the key transcription factor responsible for inducing ferroptosis remains elusive. In this study, we discovered that ATOH8 is upregulated in prostate cancer cells treated with the ferroptosis inducer. Overexpression of ATOH8 increased the vulnerability of prostate cancer to ferroptosis, while ATOH8 deletion promotes ferroptosis evasion. Mechanistically, ATOH8 suppresses the transcription of SCD, reducing the synthesis of monounsaturated fatty acids that confer resistance to ferroptosis. Additionally, ATOH8 works in conjunction with the E protein E47 to form a transcriptional repression complex that inhibits SCD transcription. Furthermore, we discovered that EZH2 epigenetically suppresses the expression of ATOH8 through DNA methylation and H3K27 methylation. Interestingly, EZH2 was found to be downregulated in ferroptosis, resulting in an upregulation of ATOH8. Pharmacological inhibition of EZH2 combined with ferroptosis inducer significantly suppresses prostate cancer growth in vitro and in vivo. Together, our findings unveil that EZH2-mediated ATOH8 downregulation promotes ferroptosis evasion and suggest that pharmacological manipulation of EZH2 and ATOH8 is a promising therapeutic strategy for prostate cancer.
2025-01-30 | GSE282996 | GEO
Project description:Ferroptosis, a non-apoptotic programmed cell death triggered by excessive iron-dependent lipid peroxidation, plays a pivotal role in tumor progression. Significant progress has been made in elucidating the role of transcription factors in the regulation of ferroptosis. Nevertheless, the identification of the key transcription factor responsible for inducing ferroptosis remains elusive. In this study, we discovered that ATOH8 is upregulated in prostate cancer cells treated with the ferroptosis inducer. Overexpression of ATOH8 increased the vulnerability of prostate cancer to ferroptosis, while ATOH8 deletion promotes ferroptosis evasion. Mechanistically, ATOH8 suppresses the transcription of SCD, reducing the synthesis of monounsaturated fatty acids that confer resistance to ferroptosis. Additionally, ATOH8 works in conjunction with the E protein E47 to form a transcriptional repression complex that inhibits SCD transcription. Furthermore, we discovered that EZH2 epigenetically suppresses the expression of ATOH8 through DNA methylation and H3K27 methylation. Interestingly, EZH2 was found to be downregulated in ferroptosis, resulting in an upregulation of ATOH8. Pharmacological inhibition of EZH2 combined with ferroptosis inducer significantly suppresses prostate cancer growth in vitro and in vivo. Together, our findings unveil that EZH2-mediated ATOH8 downregulation promotes ferroptosis evasion and suggest that pharmacological manipulation of EZH2 and ATOH8 is a promising therapeutic strategy for prostate cancer.
2025-01-30 | GSE282995 | GEO