Scholarlink

<p>The lysine-specific demethylase 1 (LSD1) regulates hematopoietic stem cell differentiation and has been identified as a therapeutic target in hematological disorders. LSD1 demethylates mono and dimethylated histones 3 at lysine 4 and 9. In addition, it acts as a scaffold for the formation of chromatin-modifying complexes that regulates the transcription of myeloid-lineage-specific genes in complex with GFI1, a transcriptional repressor. While both enzymatic and non-enzymatic functions of LSD1 have been well defined, the relative importance of these two functions in hematopoiesis remains incompletely understood. Here, we investigated the contribution of enzymatic and non-enzymatic functions of LSD1 to myelopoiesis. We show that myeloid differentiation is independent of the enzymatic functions of LSD1 but requires the non-enzymatic, scaffolding function, which directs GFI1 binding to target sequences. In the absence of the LSD1 protein, GFI1 DNA binding is diminished, and myeloid cell differentiation arrests at an immature, myelomonocytic-like cell stage, which overexpresses <i>Prtn3</i>. We provide functional data implicating <i>Prtn3</i> as an effector of the stem cell expansion and myeloid maturation block caused by the loss of LSD1.</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

Lysine-specific demethylase 1 regulates hematopoietic stem cell expansion and myeloid cell differentiation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月15日

查看全文
  • Hans Felix Staehle,
  • Christoph Koellerer,
  • Anne Marie Staehle,
  • Jana Schulze,
  • Philipp Eble,
  • Anja Müller,
  • Franziska Zell,
  • Judith M. Müller,
  • Florian Perner,
  • Aya Attia,
  • Jan-Philipp Mallm,
  • Olga Pozdnyakova,
  • Karsten Rippe,
  • Benedikt Brors,
  • Lars Feuerbach,
  • Charles D. Imbusch,
  • Eric Metzger,
  • Roland Schüle,
  • Heike L. Pahl,
  • Jonas S. Jutzi

摘要

The lysine-specific demethylase 1 (LSD1) regulates hematopoietic stem cell differentiation and has been identified as a therapeutic target in hematological disorders. LSD1 demethylates mono and dimethylated histones 3 at lysine 4 and 9. In addition, it acts as a scaffold for the formation of chromatin-modifying complexes that regulates the transcription of myeloid-lineage-specific genes in complex with GFI1, a transcriptional repressor. While both enzymatic and non-enzymatic functions of LSD1 have been well defined, the relative importance of these two functions in hematopoiesis remains incompletely understood. Here, we investigated the contribution of enzymatic and non-enzymatic functions of LSD1 to myelopoiesis. We show that myeloid differentiation is independent of the enzymatic functions of LSD1 but requires the non-enzymatic, scaffolding function, which directs GFI1 binding to target sequences. In the absence of the LSD1 protein, GFI1 DNA binding is diminished, and myeloid cell differentiation arrests at an immature, myelomonocytic-like cell stage, which overexpresses Prtn3. We provide functional data implicating Prtn3 as an effector of the stem cell expansion and myeloid maturation block caused by the loss of LSD1.