Gene expression from the imprinted Dio3 locus is associated with cell proliferation of cultured brown adipocytes
Gene expression from the imprinted Dio3 locus is associated with cell proliferation of cultured brown adipocytes
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DOI：
10.1210/en.2007-0029
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发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
Obregon, Maria-Jesus
中科院分区：
文献类型：
--
作者：
Hernandez, Arturo;Garcia, Bibian;Obregon, Maria-Jesus
活性甲状腺激素对棕色脂肪组织的分化和功能至关重要。然而，我们已经观察到高的基础和诱导水平的3型脱碘酶（D3），失活甲状腺激素的酶，是由印迹基因Dio 3编码，在分化棕色前脂肪细胞在原代培养。我们发现，D3的活性和mRNA的表达与未分化的前体细胞在各种条件下的增殖率密切相关。此外，前体细胞向脂肪细胞的分化与D3表达水平的降低相关，并且在成熟脂肪细胞中仅发现非常低水平的D3 mRNA。Dlk 1是脂肪细胞分化的抑制剂，也是位于与Dio 3相同的印迹结构域中的父系表达基因，其表达变化与Dio 3的表达变化平行。相反，Dio 3 os的4- kb转录物（也位于相同印记结构域的反义基因）在分化的脂肪细胞中显著上调。我们的结论是，D3在分化前脂肪细胞的表达主要与增殖细胞，而Dio 3 os的表达与成熟脂肪细胞。我们的研究结果表明，基因组印迹和基因表达在Dlk 1/Dio 3印迹结构域可能在脂肪细胞的增殖和分化的调节中发挥作用。
Active thyroid hormones are critical for the differentiation and function of brown adipose tissue. However, we have observed high basal and induced levels of type 3 deiodinase ( D3), an enzyme that inactivates thyroid hormones and is coded by the imprinted gene Dio3, in differentiating brown preadipocytes in primary culture. We find that D3 activity and mRNA expression strongly correlate with the rate of proliferation of undifferentiated precursor cells under various conditions. Furthermore, differentiation of precursor cells to adipocytes is associated with decreased levels of D3 expression, and only very low levels of D3 mRNA are found in mature adipocytes. Dlk1, an inhibitor of adipocyte differentiation and a paternally expressed gene located in the same imprinted domain as Dio3, displayed changes in expression that parallel those of Dio3. In contrast, a 4- kb transcript for Dio3os, an antisense gene also located in the same imprinted domain, is markedly up- regulated in differentiated adipocytes. We conclude that D3 expression in differentiating preadipocytes is primarily linked to proliferating cells, whereas Dio3os expression is associated with mature adipocytes. Our results suggest that genomic imprinting and gene expression at the Dlk1/ Dio3 imprinted domain may play a role in the regulation of adipocyte proliferation and differentiation.