Scholarlink

<p>The basic leucine zipper ATF-like transcription factor 3 (BATF3) has been implicated in the pathogenesis of type 1 diabetes mellitus (T1DM), where it may influence immune regulation and pancreatic β-cell homeostasis. Nevertheless, the upstream molecular mechanisms governing BATF3 expression remain largely undefined. Bioinformatic analyses of GEO and UCSC databases were conducted to identify transcription factors potentially regulating BATF3 (GEO: GSE9006 PBMC microarray; newly diagnosed T1D, <i>n</i> = 43; healthy controls, <i>n</i> = 24). Clinical samples (PBMC, <i>n</i> = 30) from T1DM patients and healthy controls were analyzed by qPCR to assess BATF3 and candidate transcription factor expression. Lentiviral transduction and siRNA-mediated knockdown were applied to examine BATF3 regulation and its impact on CD8⁺ T-cell function. Transcription factor–promoter interactions were validated using dual-luciferase reporter assays and ChIP-qPCR. EGR1, EGR2, EGR3, and c-MYC were identified as differentially expressed transcription factors in GSE9006, with c-MYC emerging as the central regulator. Clinical analysis demonstrated significantly elevated expression of c-MYC and BATF3 in T1DM patients compared with healthy controls (<i>n</i> = 30, <i>p</i> &lt; 0.05). In vitro assays confirmed that c-MYC binds to the BATF3 promoter region approximately 1–2&#xa0;kb upstream of the transcription start site, thereby promoting BATF3 transcription, enhancing CD8⁺ T-cell proliferation, and inhibiting apoptosis (CD8⁺ T cells isolated from PBMCs of healthy children). ChIP-qPCR further localized the primary c-MYC binding site to the − 1,214 to − 1,203&#xa0;bp region relative to the BATF3 transcription start site. c-MYC, a critical regulator of BATF3, is markedly elevated in T1DM patients. By driving BATF3 transcription, it promotes CD8⁺ T-cell expansion and limits apoptosis, jointly contributing to pediatric T1DM pathogenesis. These observations highlight the c-MYC–BATF3 axis as a mechanistic pathway relevant to pediatric T1DM and a potential biomarker framework.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

c-MYC enhances transcription of the type 1 diabetes mellitus associated gene BATF3 via promoter binding

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月25日

查看全文
  • Ying Zhao,
  • Zhicheng Tang,
  • Ying Tao,
  • Sihui Zhao,
  • Qijie Ding,
  • Weixia Yang

摘要

The basic leucine zipper ATF-like transcription factor 3 (BATF3) has been implicated in the pathogenesis of type 1 diabetes mellitus (T1DM), where it may influence immune regulation and pancreatic β-cell homeostasis. Nevertheless, the upstream molecular mechanisms governing BATF3 expression remain largely undefined. Bioinformatic analyses of GEO and UCSC databases were conducted to identify transcription factors potentially regulating BATF3 (GEO: GSE9006 PBMC microarray; newly diagnosed T1D, n = 43; healthy controls, n = 24). Clinical samples (PBMC, n = 30) from T1DM patients and healthy controls were analyzed by qPCR to assess BATF3 and candidate transcription factor expression. Lentiviral transduction and siRNA-mediated knockdown were applied to examine BATF3 regulation and its impact on CD8⁺ T-cell function. Transcription factor–promoter interactions were validated using dual-luciferase reporter assays and ChIP-qPCR. EGR1, EGR2, EGR3, and c-MYC were identified as differentially expressed transcription factors in GSE9006, with c-MYC emerging as the central regulator. Clinical analysis demonstrated significantly elevated expression of c-MYC and BATF3 in T1DM patients compared with healthy controls (n = 30, p < 0.05). In vitro assays confirmed that c-MYC binds to the BATF3 promoter region approximately 1–2 kb upstream of the transcription start site, thereby promoting BATF3 transcription, enhancing CD8⁺ T-cell proliferation, and inhibiting apoptosis (CD8⁺ T cells isolated from PBMCs of healthy children). ChIP-qPCR further localized the primary c-MYC binding site to the − 1,214 to − 1,203 bp region relative to the BATF3 transcription start site. c-MYC, a critical regulator of BATF3, is markedly elevated in T1DM patients. By driving BATF3 transcription, it promotes CD8⁺ T-cell expansion and limits apoptosis, jointly contributing to pediatric T1DM pathogenesis. These observations highlight the c-MYC–BATF3 axis as a mechanistic pathway relevant to pediatric T1DM and a potential biomarker framework.