Defects in lamin B1 expression or processing affect interphase chromosome position and gene expression.

Defects in lamin B1 expression or processing affect interphase chromosome position and gene expression.
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层粘连蛋白B1表达或加工的缺陷会影响相间染色体的位置和基因表达。

DOI:
10.1083/jcb.200607054
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发表时间:
2007-02-26
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Vaux DJ
Vaux DJ
中科院分区:
其他
文献类型:
--
作者:
Malhas A;Lee CF;Sanders R;Saunders NJ;Vaux DJ

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具有外围基因贫乏染色体和中心基因丰富染色体的细胞核的放射状组织很常见,并且可能依赖于核边界作为支架或位置标记。为了测试这一点,我们研究了普遍存在的核膜 (NE) 成分核纤层蛋白 B1 在 NE 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内切蛋白水解(通过 Rce1),而不是羧甲基化(通过 Icmt),而核纤层蛋白 C 层稳定性不受全长核纤层蛋白 B1 或其加工损失的影响。将野生型小鼠成纤维细胞与缺乏全长核纤层蛋白 B1 或 CAAX 加工缺陷的成纤维细胞进行比较,鉴定出依赖稳定加工的核纤层蛋白 B1 核纤层进行正常表达的基因。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种稳定的核纤层。结果表明加工后的核纤层蛋白 B1 参与基因表达和染色体位置的控制。
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.
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