Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment.
Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment.
复制标题
鉴定锌指蛋白 Bcl6 作为早期脂肪形成的新型调节剂
DOI：
10.1098/rsob.160065
复制
发表时间：
2016-06
期刊：
影响因子：
5.8
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Hu X;Zhou Y;Yang Y;Peng J;Song T;Xu T;Wei H;Jiang S;Peng J
脂肪组织是全身代谢和能量稳态的关键决定因素。因此，从生物医学的角度来看，阐明脂肪生成过程中的转录调控过程具有高度相关性。在这些研究中，锌指蛋白 B 细胞淋巴瘤 6 (Bcl6) 被证明在间充质干细胞的早期脂肪形成中发挥作用。与非前脂肪成纤维细胞相比，Bcl6 在前脂肪细胞中富集，并在脂肪形成的早期阶段表达上调。功能获得和功能丧失研究表明，Bcl6 在体外和离体中充当脂肪定型和分化的关键调节因子。 C3H10T1/2 细胞中 RNAi 介导的 Bcl6 敲低极大地抑制了成脂潜力，而 Bcl6 过表达则增强了成脂分化。该转录因子还直接或间接靶向和控制一些早期和晚期脂肪形成调节因子（即 Zfp423、Zfp467、KLF15、C/EBPδ、C/EBPα 和 PPARγ）的表达。我们进一步确定 Bcl6 反式激活信号转导子和转录激活子 1 (STAT1)，这被确定为脂肪形成所需的因子。此外，STAT1的过表达挽救了C3H10T1/2细胞中由Bcl6敲低引起的脂肪形成定向和分化的损害，从而证实STAT1是Bcl6的下游直接靶标。这项研究确定 Bcl6 是早期脂肪形成的正转录调节因子。
Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo. RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation. This transcription factor also directly or indirectly targets and controls the expression of some early and late adipogenic regulators (i.e. Zfp423, Zfp467, KLF15, C/EBPδ, C/EBPα and PPARγ). We further identified that Bcl6 transactivated the signal transducers and activators of transcription 1 (STAT1), which was determined as a required factor for adipogenesis. Moreover, overexpression of STAT1 rescued the impairment of adipogenic commitment and differentiation induced by Bcl6 knockdown in C3H10T1/2 cells, thereby confirming that STAT1 is a downstream direct target of Bcl6. This study identifies Bcl6 as a positive transcriptional regulator of early adipose commitment.