Hmgb1 can facilitate activation of the matrilin-1 gene promoter by Sox9 and L-Sox5/Sox6 in early steps of chondrogenesis

Szénási, Tibor; Kenesi, Erzsébet; Nagy, Andrea; Molnár, Annamária; Bálint, Bálint László; Zvara, Ágnes; Csabai, Zsolt; Deák, F.; Oláh, Beáta Boros; Mátés, Lajos; Nagy, László; Puskás, László G.; Kiss, Ibolya

doi:10.1016/j.bbagrm.2013.07.004

Cited by 9 publications

(7 citation statements)

References 59 publications

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“…49 For example, HMGB1 recruits the SOX trio (Sox9, L-Sox5/Sox6) to the cartilage matrix protein Matn1 gene promoter, facilitating activation of Matn1. 22 HMGB1 also interacts with p53 and mediates p53-dependent transactivation of such genes as p21/WAF1. 48,50 HMGB1 binds to the HOX family and the Rel family transcription factors by interacting with the homeodomain of HOX proteins and p50 subunit of the Rel proteins, respectively, via the HMG box.…”

Section: Discussionmentioning

confidence: 99%

“…1,4,5 The high mobility group box 1 gene (HMGB1) could recruit the chondrogenic SOX trio (Sox9, L-Sox5/Sox6) to the matrilin-1 gene (Matn1) promoter, facilitating activation of Matn1 in early chondrogenesis by promoting DNA-protein interactions and DNA bending. 22 HMGB3, another member of ΗΜGB family, is homologous to HMGB1 23 and is overexpressed in such solid tumors as ovarian cancer, colorectal cancer, and PCa. [24][25][26] In our preliminary experiments, we noticed HMGB3 might regulate downstream targets of SOX9, such as BMI-1.…”

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confidence: 99%

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SOX9 and HMGB3 co‐operatively transactivate NANOG and promote prostate cancer progression

et al. 2022

The Prostate

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Background: The homeodomain-containing transcription factor NANOG is overexpressed in prostate adenocarcinoma (PCa) and predicts poor prognosis. The SOX family transcription factor SOX9, as well as the transcription co-activator HMGB3 of the HMGB family, are also overexpressed and may play pivotal roles in PCa.However, it is unknown whether SOX9 and HMGB3 interact with each other, or if they regulate NANOG gene transcription. Methods: We identified potential SOX9 responsive elements in NANOG promoter, and investigated if SOX9 regulated NANOG transcription in co-operation with HMGB3 by experimental analysis of potential SOX9 binding sites in NANOG promoter, reporter gene transcription assays with or without interference or artificial overexpression of SOX9 and/or HMGB3, and protein-binding assays of SOX9-HMGB3 interaction. Clinicopathologic and prognostic significance of SOX9-HMGB3 overexpression in PCa was analyzed. Results: SOX9 activated NANOG gene transcription by preferentially binding to a highly conserved consensus cis-regulatory element (−573 to −568) in NANOG promoter, and promoted the expression of NANOG downstream oncogenic genes. Importantly, HMGB3 functioned as a partner of SOX9 to co-operatively enhance transactivation of NANOG by interacting with SOX9, predominantly via the HMG Box A domain of HMGB3. Overexpression of SOX9 and/or HMGB3 enhanced PCa cell survival and cell migration and were significantly associated with PCa progression. Notably, Cox proportional regression analysis showed that co-overexpression of both SOX9 and HMGB3 was an independent unfavorable prognosticator for both CRPC-free survival (relative risk [RR] = 3.779，95% confidence interval [CI]: 1.159-12.322, p = 0.028) and overall survival (RR = 3.615， 95% CI: 1.101-11.876, p = 0.034).Conclusions: These findings showed a novel SOX9/HMGB3/NANOG regulatory mechanism, deregulation of which played important roles in PCa progression.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

SOX9 and HMGB3 co‐operatively transactivate NANOG and promote prostate cancer progression

et al. 2022

The Prostate

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“…HMGB1 assists other molecules such as organic cation/carnitine transporter1/2 and p53 to bind to target genes and facilitates DNA modification [ 39 , 40 ]. HMGB1 could boost the Matn1 promoter activity via SRY-related high-mobility group box (SOX) trio in early chondrogenesis, and the binding efficiency of SOX trio in Matn1 promoter could be affected by HMGB1 [ 41 ]. Furthermore, HMGB1 formed complexes with proinflammatory factors to involve in inflammatory pathologies [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4⁺ T Cells from aGVHD Patients

Chen

Liu

et al. 2020

Journal of Immunology Research

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STAT3 is highly expressed in aGVHD CD4+ T cells and plays a critical role in inducing or worsening aGVHD. In our preceding studies, DNA hypomethylation in STAT3 promoter was shown to cause high expression of STAT3 in aGVHD CD4+ T cells, and the process could be modulated by HMGB1, but the underlying mechanism remains unclear. TET2, AID, and TDG are indispensable in DNA demethylation; meanwhile, TET2 and AID also serve extremely important roles in immune response. So, we speculated these enzymes involved in the STAT3 promoter hypomethylation induced by HMGB1 in aGVHD CD4+ T cells. In this study, we found that the binding levels of TET2/AID/TDG to STAT3 promoter were remarkably increased in CD4+T cells from aGVHD patients and were significantly negatively correlated with the STAT3 promoter methylation level. Simultaneously, we revealed that HMGB1 could recruit TET2, AID, and TDG to form a complex in the STAT3 promoter region. Interference with the expression of TET2/AID/TDG inhibited the overexpression of STAT3 caused by HMGB1 downregulation of the STAT3 promoter DNA methylation. These data demonstrated a new molecular mechanism of how HMGB1 promoted the expression of STAT3 in CD4+ T cells from aGVHD patients.

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“…High mobility group box 1 (HMGB1) is a nuclear binding protein that acts as an extracellular pro-inflammatory cytokine that has been implicated in high-level expression in several malignancies [4]. Furthermore, in HMG-box family proteins, a canonical HMGB1 protein has a distinctly related DNA-binding domain regulating gene expression with a Sry-related high mobility group box 9 (SOX9) protein using distinct mechanisms [5]. The transcription factor SOX9 plays a vital role in embryonic development and is highly expressed in various tumors, such as prostate, non-small cell lung, and breast cancers [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage

Suwannakul

Midorikawa

et al. 2021

Discov Onc

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Cholangiocarcinoma (CCA) is a malignant disease with a poor prognosis, and several studies have been conducted using different molecular markers as a tool for CCA diagnosis, including Clonorchis sinensis (CS)-CCA. We initially identified the expression profiles of the three markers of interest, HMGB1, SOX9, and YAP1, using GSE (GSE76297 and GSE32958) datasets. Upregulated levels of these three proteins were detected in CCA samples compared to those in normal samples. To clarify this issue, 24 human CCA tissues with paired adjacent normal tissues were evaluated using immunohistochemical staining. Of the three markers, the total cellular staining intensities were scanned, and subcellular localization was scored in the nuclear and cytoplasmic regions. The intensities of HMGB1, SOX9, and YAP1 were elevated in CCA tissues than the adjacent normal tissues. Individual scoring of subcellular localization revealed that the expression levels of HMGB1 (nucleus) and YAP1 (nucleus and cytoplasm) were significantly different from the pathologic M stage. Moreover, the translocation pattern was categorized using “site-index”, and the results demonstrated that the overexpression of HMGB1 and SOX9 was mostly observed in both the nucleus and cytoplasm, whereas YAP1 was predominantly expressed in the cytoplasm of tumor cells. Interestingly, the site index of HMGB1 was moderately correlated with the tumor stage (r = 0.441, p = 0.031). These findings imply that the overexpression of subcellular HMGB1 could be associated with the metastatic status of patients with CS-CCA, which was shown to be effective for CS-CCA prognosis.

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Hmgb1 can facilitate activation of the matrilin-1 gene promoter by Sox9 and L-Sox5/Sox6 in early steps of chondrogenesis

Cited by 9 publications

References 59 publications

SOX9 and HMGB3 co‐operatively transactivate NANOG and promote prostate cancer progression

SOX9 and HMGB3 co‐operatively transactivate NANOG and promote prostate cancer progression

HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4⁺ T Cells from aGVHD Patients

Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage

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Hmgb1 can facilitate activation of the matrilin-1 gene promoter by Sox9 and L-Sox5/Sox6 in early steps of chondrogenesis

Cited by 9 publications

References 59 publications

SOX9 and HMGB3 co‐operatively transactivate NANOG and promote prostate cancer progression

SOX9 and HMGB3 co‐operatively transactivate NANOG and promote prostate cancer progression

HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients

Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage

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HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4⁺ T Cells from aGVHD Patients