PRDM16 function in neural development

共价组蛋白修饰的表观遗传调控在决定发育中起着重要作用 过程和细胞命运的决定。它补充了遗传信息，并提供了额外的监管 在发育过程中对快速变化的细胞和组织环境做出反应的机制。近期 研究表明，组蛋白修饰酶的突变通常会扭曲正常发育的“路线图”， 从而导致人类疾病。PRDM16在维持包括神经干细胞在内的多种成体干细胞的动态平衡中起着重要作用。重要的是，小鼠Prdm16基因的缺失会导致多种脑缺陷，包括小头畸形、大脑皮层受损和胼胝体发育不全。然而，目前还不清楚PRDM16如何调节神经前体细胞的功能，以及它的缺失如何导致正常神经发生的中断。我们有 新近发现，PRDM16是一种组蛋白甲基转移酶，可使组蛋白H3甲基化。这一发现链接到 PRDM16缺失导致神经干细胞表观遗传修饰的解除调控，这些修饰在 定义干细胞中定义细胞身份的转录电路。

Epigenetic regulation via covalent histone modifications plays an important role in dictating developmental processes and cell fate determination. It complements to genetic information and provides additional regulatory mechanisms in response to fast changing cellular and organismal environment during development. Recent studies show that mutations in histone modifying enzymes often skew the normal development ‘roadmap’ and consequently lead to human diseases. PRDM16 plays an important role in maintaining homeostasis of multiple adult stem cells including neural stem cells. Importantly, Prdm16 deletion in mice leads to multiple brain defects including microcephaly, disrupted cerebral cortex and agenesis of the corpus callosum. However, it remains unclear how PRDM16 regulate functions of neural progenitor cells and how its deletion leads to disruption of normal neurogenesis. We have recently found that PRDM16 is a histone methyltransferase that methylate histone H3. This finding links PRDM16 deletion to deregulation of epigenetic modifications in neural stem cells, which play essential roles in define transcription circuitries in stem cells that define cellular identity.