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<p>Polycomb Repressive Complex 1 (PRC1) is a group of epigenetic regulatory complexes critical for mammalian development. Elucidating PRC1 composition and function across cell types and developmental stages is key to understanding the epigenetic regulation of cell fate determination. In this study, we discovered POGZ, a prominent autism spectrum disorder (ASD) risk factor, as a novel component of PRC1.6, forming the PRC1.6-POGZ complex. Functional assays revealed that POGZ elicits transcriptional repression that is dependent on RING1B expression. Analysis of publicly available data showed that POGZ highly colocalizes with RING1B and HP1g, two PRC1.6 components, at genes involved in multiple aspects of transcriptional regulation in embryonic mouse cortical cells. Although <i>Pogz</i> knockout (KO) does not compromise stem cell pluripotency, <i>Pogz</i> ablation in neuronal progenitor cells (NPCs) led to widespread transcriptomic dysregulation with failed activation of key neuronal genes. Finally, we demonstrated that PRC1.6-POGZ regulates neuronal differentiation by repressing bone morphogenetic protein (BMP) signaling. These findings reveal a mechanism by which PRC1 and POGZ coordinate transcription during neuronal differentiation and demonstrate that disrupting this complex impairs BMP signaling, potentially contributing to neurodevelopmental disorders such as ASD.</p>

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The Zinc-Finger Protein POGZ Associates with Polycomb Repressive Complex 1 to Regulate Bone Morphogenetic Protein Signaling During Neuronal Differentiation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月2日

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  • Jessenia Chavez,
  • Trevor Wolf,
  • Cynthia Lascarez Espana,
  • Zhuangzhuang Geng,
  • Yen Teng Tai,
  • John Flanagan,
  • George-Lucian Moldovan,
  • James Stafford,
  • Zhonghua Gao

摘要

Polycomb Repressive Complex 1 (PRC1) is a group of epigenetic regulatory complexes critical for mammalian development. Elucidating PRC1 composition and function across cell types and developmental stages is key to understanding the epigenetic regulation of cell fate determination. In this study, we discovered POGZ, a prominent autism spectrum disorder (ASD) risk factor, as a novel component of PRC1.6, forming the PRC1.6-POGZ complex. Functional assays revealed that POGZ elicits transcriptional repression that is dependent on RING1B expression. Analysis of publicly available data showed that POGZ highly colocalizes with RING1B and HP1g, two PRC1.6 components, at genes involved in multiple aspects of transcriptional regulation in embryonic mouse cortical cells. Although Pogz knockout (KO) does not compromise stem cell pluripotency, Pogz ablation in neuronal progenitor cells (NPCs) led to widespread transcriptomic dysregulation with failed activation of key neuronal genes. Finally, we demonstrated that PRC1.6-POGZ regulates neuronal differentiation by repressing bone morphogenetic protein (BMP) signaling. These findings reveal a mechanism by which PRC1 and POGZ coordinate transcription during neuronal differentiation and demonstrate that disrupting this complex impairs BMP signaling, potentially contributing to neurodevelopmental disorders such as ASD.