Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Brain Tumor Center, Cincinnati Children's Hospital Medical Center, OH, USA.
FEBS Lett. 2018 Apr;592(7):1063-1078. doi: 10.1002/1873-3468.12999. Epub 2018 Feb 22.
Myelination by oligodendrocytes in the central nervous system permits high-fidelity saltatory conduction from neuronal cell bodies to axon terminals. Dysmyelinating and demyelinating disorders impair normal nervous system functions. Consequently, an understanding of oligodendrocyte differentiation that moves beyond the genetic code into the field of epigenetics is essential. Chromatin reprogramming is critical for steering stage-specific differentiation processes during oligodendrocyte development. Fine temporal control of chromatin remodeling through ATP-dependent chromatin remodelers and sequential histone modifiers shapes a chromatin regulatory landscape conducive to oligodendrocyte fate specification, lineage differentiation, and maintenance of cell identity. In this Review, we will focus on the biological functions of ATP-dependent chromatin remodelers and histone deacetylases in myelinating oligodendrocyte development and implications for myelin regeneration in neurodegenerative diseases.
中枢神经系统中的少突胶质细胞的髓鞘形成允许从神经元细胞体到轴突末端进行高保真的跳跃传导。脱髓鞘和脱髓鞘疾病会损害正常的神经系统功能。因此,理解超越遗传密码进入表观遗传学领域的少突胶质细胞分化至关重要。染色质重编程对于指导少突胶质细胞发育过程中的阶段特异性分化过程至关重要。通过 ATP 依赖性染色质重塑酶和顺序组蛋白修饰剂对染色质重塑进行精细的时间控制,形成有利于少突胶质细胞命运特化、谱系分化和细胞身份维持的染色质调控景观。在这篇综述中,我们将重点讨论 ATP 依赖性染色质重塑酶和组蛋白去乙酰化酶在髓鞘形成少突胶质细胞发育中的生物学功能,以及它们对神经退行性疾病中髓鞘再生的影响。