Margalit Ayelet, Neufeld Esther, Feinstein Naomi, Wilson Katherine L, Podbilewicz Benjamin, Gruenbaum Yosef
Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
J Cell Biol. 2007 Aug 13;178(4):661-73. doi: 10.1083/jcb.200704049.
Barrier to autointegration factor (BAF) binds double-stranded DNA, selected histones, transcription regulators, lamins, and LAP2-emerin-MAN1 (LEM) domain proteins. During early Caenorhabditis elegans embryogenesis, BAF-1 is required to organize chromatin, capture segregated chromosomes within the nascent nuclear envelope, and assemble lamin and LEM domain proteins in reforming nuclei. In this study, we used C. elegans with a homozygous deletion of the baf-1 gene, which survives embryogenesis and larval stages, to report that BAF-1 regulates maturation and survival of the germline, cell migration, vulva formation, and the timing of seam cell fusion. In the seam cells, BAF-1 represses the expression of the EFF-1 fusogen protein, but fusion still occurs in C. elegans lacking both baf-1 and eff-1. This suggests the existence of an eff-1-independent mechanism for cell fusion. BAF-1 is also required to maintain the integrity of specific body wall muscles in adult animals, directly implicating BAF in the mechanism of human muscular dystrophies (laminopathies) caused by mutations in the BAF-binding proteins emerin and lamin A.
自身整合因子屏障（BAF）可结合双链DNA、特定组蛋白、转录调节因子、核纤层蛋白以及LAP2-emerin-MAN1（LEM）结构域蛋白。在秀丽隐杆线虫胚胎发育早期，BAF-1对于染色质的组织、在新生核膜内捕获分离的染色体以及在重新形成的细胞核中组装核纤层蛋白和LEM结构域蛋白是必需的。在本研究中，我们使用了baf-1基因纯合缺失的秀丽隐杆线虫，其能在胚胎发育和幼虫阶段存活，以报告BAF-1调节生殖系的成熟和存活、细胞迁移、外阴形成以及接缝细胞融合的时间。在接缝细胞中，BAF-1抑制EFF-1融合蛋白的表达，但在同时缺乏baf-1和eff-1的秀丽隐杆线虫中仍会发生融合。这表明存在一种不依赖eff-1的细胞融合机制。BAF-1对于维持成年动物特定体壁肌肉的完整性也是必需的，这直接表明BAF参与了由BAF结合蛋白emerin和核纤层蛋白A突变引起的人类肌肉营养不良（核纤层病）的发病机制。
