The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice
The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice
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DOI：
10.1038/10338
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发表时间：
1999-07-01
期刊：
影响因子：
30.8
通讯作者：
Bianchi, ME
中科院分区：
文献类型：
--
作者：
Calogero, S;Grassi, F;Bianchi, ME
高迁移率族1（HMG 1）蛋白是所有哺乳动物细胞核中丰富的组分，并且相关蛋白存在于所有真核生物中（1，2）。HMG 1以中等亲和力结合线性DNA，无序列特异性（3），但在通过小沟结合时显著弯曲双螺旋（4）。它以高亲和力与已经急剧弯曲的DNA结合，例如核小体入口和出口处的接头DNA（5-7）;因此，它被认为是染色质的结构蛋白，HMG 1也通过与所需蛋白质相互作用被募集到DNA中，用于基础和调节性转录（8-13）和V（D）J重组（14，15）。在这里，我们产生了Hmg 1缺失的小鼠。Hmg 1（-/-）幼仔出生时是活的，但在24小时内死于低血糖，如果胃肠外给予葡萄糖，Hmg 1缺陷小鼠存活数天，然后因多效性缺陷而消瘦（但免疫库没有改变）。缺乏Hmg 1的细胞系生长正常，但糖皮质激素受体（GR，由基因Grl 1编码）对基因表达的激活受损。因此，Hmg 1对于细胞核中染色质的整体组织不是必需的，但对于特定转录因子的适当转录控制是至关重要的。
High mobility group 1 (HMG1) protein is an abundant component of all mammalian nuclei, and related proteins exist in all eukaryotes(1,2). HMG1 binds linear DNA with moderate affinity and no sequence specificity(3), but bends the double helix significantly on binding through the minor groove(4). It binds with high affinity to DNA that is already sharply bent, such as linker DNA at the entry and exit of nucleosomes(5-7); thus, it is considered a structural protein of chromatin, HMG1 is also recruited to DNA by interactions with proteins required,for basal and regulated transcriptions(8-13) and V(D)J recombination(14,15). Here we generate mice harbouring deleted Hmg1. Hmg1(-/-) pups are born alive, hut die within 24 hours due to hypoglycaemia, Hmg1-deficient mice survive for several days if given glucose parenterally, then waste away with pleiotropic defects (but no alteration in the immune repertoire). Cell lines lacking Hmg1 grow normally, but the activation of gene expression by the glucocorticoid receptor (GR, encoded by the gene Grl1) is impaired. Thus, Hmg1 is not essential for the overall organization of chromatin in the cell nucleus, but is critical for proper transcriptional control by specific transcription factors.