Genome-wide survey and functional analysis reveal TCF21 promotes chicken preadipocyte differentiation by directly upregulating HTR2A
Genome-wide survey and functional analysis reveal TCF21 promotes chicken preadipocyte differentiation by directly upregulating HTR2A
复制标题
全基因组调查和功能分析揭示TCF21通过直接上调HTR2A促进鸡前脂肪细胞分化
DOI：
10.1016/j.bbrc.2021.11.103
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发表时间：
2022
影响因子：
3.1
通讯作者：
Hui Li
中科院分区：
文献类型：
--
作者：
Xinyang Zhang;Bohan Cheng;Yanyan Ma;Yumeng Liu;Ning Wang;Hui Zhang;Yumao Li;Yuxiang Wang;Peng Luan;Zhiping Cao;Hui Li
以前，我们发现转录因子21（TCF 21）促进鸡前脂肪细胞分化。然而，TCF 21在鸡脂肪形成过程中的全基因组结合位点及其下游靶基因尚不清楚。应用qPCR和荧光素酶报告基因分析验证测序结果。采用Western blotting、油红O染色和药物处理等方法，对TCF 21的直接下游结合靶点5-羟色胺受体2A（HTR 2A）的功能进行了研究。ChIP-qPCR、RT-qPCR和荧光素酶报告基因分析表明，HTR 2A是TCF 21的真正直接下游结合靶点之一。脂肪系肉鸡脂肪组织中HTR 2A的表达上调。此外，在脂肪形成过程中，HTR 2A的丰度逐渐增加。有趣的是，HTR 2A的药理学增强或抑制分别促进或减弱前脂肪细胞的分化。此外，HTR 2A抑制受损的TCF 21 promoted adipogenesization.ConclusionsWe分析了全基因组TCF 21的结合位点在鸡分化的前脂肪细胞揭示HTR 2A作为直接下游目标的TCF 21在脂肪形成。
Background/aimPreviously, we showed that transcription factor 21 (TCF21) promotes chicken preadipocyte differentiation. However, the genome-wide TCF21 binding sites and its downstream target genes in chicken adipogenesis were unknown.MethodsChIP-Seq and RNA-Seq were used to screen candidate targets of TCF21. qPCR and luciferase reporter assay were applied to verify the sequencing results. Western blotting, oil red-O staining and pharmacological treatments were performed to investigate the function of 5-hydroxytryptamine receptor 2A (HTR2A), one of the bonafide direct downstream binding targets of TCF21.ResultsA total of 94 candidate target genes of TCF21 were identified. ChIP-qPCR, RT-qPCR, and luciferase reporter assay demonstrated that HTR2A is one of the bonafide direct downstream binding targets of TCF21. HTR2A expression in adipose tissue was upregulated in fat line broilers. Also, the abundance of HTR2A gradually increased during the adipogenesis process. Interestingly, pharmacological enhancement or inhibition of HTR2A promoted or attenuated the differentiation of preadipocytes, respectively. Furthermore, HTR2A inhibition impaired the TCF21 promoted adipogenesis.ConclusionsWe profiled the genome-wide TCF21 binding sites in chicken differentiated preadipocytes revealing HTR2A as the direct downstream target of TCF21 in adipogenesis.