Malhas Ashraf, Lee Chiu Fan, Sanders Rebecca, Saunders Nigel J, Vaux David J
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England, UK.
J Cell Biol. 2007 Feb 26;176(5):593-603. doi: 10.1083/jcb.200607054. Epub 2007 Feb 20.
Radial organization of nuclei with peripheral gene-poor chromosomes and central gene-rich chromosomes is common and could depend on the nuclear boundary as a scaffold or position marker. To test this, we studied the role of the ubiquitous nuclear envelope (NE) component lamin B1 in NE stability, chromosome territory position, and gene expression. The stability of the lamin B1 lamina is dependent on lamin endoproteolysis (by Rce1) but not carboxymethylation (by Icmt), whereas lamin C lamina stability is not affected by the loss of full-length lamin B1 or its processing. Comparison of wild-type murine fibroblasts with fibroblasts lacking full-length lamin B1, or defective in CAAX processing, identified genes that depend on a stable processed lamin B1 lamina for normal expression. We also demonstrate that the position of mouse chromosome 18 but not 19 is dependent on such a stable nuclear lamina. The results implicate processed lamin B1 in the control of gene expression as well as chromosome position.
细胞核中基因贫乏的染色体位于外周、基因丰富的染色体位于中央的径向组织是常见的，并且可能依赖于核边界作为支架或位置标记。为了验证这一点，我们研究了普遍存在的核膜（NE）成分核纤层蛋白B1在核膜稳定性、染色体区域位置和基因表达中的作用。核纤层蛋白B1层的稳定性取决于核纤层蛋白的内蛋白水解作用（由Rce1介导），而不依赖于羧甲基化作用（由Icmt介导），而核纤层蛋白C层的稳定性不受全长核纤层蛋白B1缺失或其加工过程的影响。将野生型小鼠成纤维细胞与缺乏全长核纤层蛋白B1或CAAX加工有缺陷的成纤维细胞进行比较，确定了正常表达依赖于稳定加工的核纤层蛋白B1层的基因。我们还证明，小鼠18号染色体而非19号染色体的位置依赖于这样一个稳定的核纤层。结果表明，加工后的核纤层蛋白B1参与了基因表达以及染色体位置的调控。
