The Myc- associated zinc finger protein epigenetically controls expression of interferon-γ-stimulated genes by recruiting STAT1 to chromatin

• 成果类型: Article
• 署名作者: Xiao, Tiaojiang; Li, Xin; Felsenfeld, Gary
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9125
• DOI: 10.1073/pnas.2320938121
• 发表日期: 2024-04-23
• 关键词: insulation; maz

摘要

The MYC - Associated Zinc Finger Protein (MAZ) plays important roles in chromatin organization and gene transcription regulation. Dysregulated expression of MAZ causes diseases, such as glioblastoma, breast cancer, prostate cancer, and liposarcoma. Previously, it has been reported that MAZ controls the proinflammatory response colitis and colon cancer via STAT3 signaling, suggesting that MAZ is involved in ulating immunity - related pathways. However, the molecular mechanism underlying this regulation remains elusive. Here, we investigate the regulatory effect of MAZ interferon - gamma (IFN -gamma ) - stimulated genes via STAT1, a protein that plays an essential role in immune responses to viral, fungal, and mycobacterial pathogens. We demonstrate that about 80% of occupied STAT1 - binding sites colocalize with occupied MAZ - binding sites in HAP1/K562 cells after IFN - gamma stimulation. MAZ depletion significantly reduces STAT1 binding in the genome. By analyzing genome - wide gene expression profiles in the RNA - Seq data, we show that MAZ depletion significantly suppresses a subset of the immune response genes, which include the IFN - stimulated genes IRF8 Absent in Melanoma 2. Furthermore, we find that MAZ controls expression of immunity - related genes by changing the epigenetic landscape in chromatin. Our reveals an important role for MAZ in regulating immune - related gene expression.