A novel candidate gene CLN8 regulates fat deposition in avian.
A novel candidate gene CLN8 regulates fat deposition in avian.
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DOI：
10.1186/s40104-023-00864-x
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发表时间：
2023-05-01
影响因子：
7
通讯作者：
Hou, Zhuocheng
中科院分区：
文献类型：
--
作者：
Li, Xiaoqin;Zhang, Fan;Sun, Yunxiao;Sun, Dandan;Yang, Fangxi;Liu, Yongtong;Hou, Zhuocheng
脂肪沉积对肉鸭风味具有重要影响，而与脂肪沉积相关的性状对肉鸭育种具有重要意义。禽脂肪相关性状是典型的复杂表型，需要大量的数据进行遗传位点分析。在本研究中，我们对1，246只鸭进行了新的脂肪性状表型分析和全基因组变异的基因分型，并与先前的GWAS数据进行了梳理，以达到1，880只鸭进行后续分析。测定各鸭的胴体组成、皮下脂肪重（SFW）、皮下脂肪率（SFP）、腹脂重（AFW）、腹脂率（AFP）和42日龄体重（BW 42）。我们发现了一组影响禽类脂肪沉积相关性状的新基因座。在这些基因座中，蜡样脂褐质沉积症，神经元8（CLN 8）是一个新的候选基因控制脂肪沉积。我们研究了其在禽类脂肪形成中的新功能和调控。在CLN 8的上游检测到5个显著的SNP（最显著的SNP，P值= 21.37E-12）和1个单倍型，用于皮下脂肪百分比。随后，荧光素酶检测表明，CLN 8基因上游的5个连锁SNP显著降低了CLN 8的转录活性。此外，ATAC-seq分析表明，在接近单倍型的区域中鉴定了转录因子结合位点。构建了一组含有CLN 8启动子不同缺失片段的荧光素酶报告基因载体，并最终在5′侧翼序列的− 1，884/− 1，207 bp区域鉴定了CLN 8的核心启动子区域，该区域含有脂肪生成相关转录因子结合位点。此外，CLN 8的过表达可以显著促进ICP中的脂肪细胞分化。与这些一致，细胞系中过表达的CLN 8的全局转录组谱分析和功能分析进一步揭示了脂肪形成期间的脂质生物合成过程显著富集。我们的研究结果表明，CLN 8是一个积极的调节禽脂肪细胞分化。这些发现证实了CLN 8在脂肪细胞分化中的新功能，为进一步研究禽类脂肪沉积机制提供了重要线索。在线版本包含补充材料，可通过10.1186/s40104-023-00864-x获得。
The fat deposition has a crucial role in animal meat flavor, and fat deposition-related traits are vital for breeding in the commercial duck industry. Avian fat-related traits are typical complex phenotypes, which need a large amount of data to analyze the genetic loci. In this study, we performed a new phenotypic analysis of fat traits and genotyped whole-genome variations for 1,246 ducks, and combed with previous GWAS data to reach 1,880 ducks for following analysis. The carcass composition traits, subcutaneous fat weight (SFW), subcutaneous fat percentage (SFP), abdominal fat weight (AFW), abdominal fat percentage (AFP) and the body weight of day 42 (BW42) for each duck were collected. We identified a set of new loci that affect the traits related to fat deposition in avian. Among these loci, ceroid-lipofuscinosis, neuronal 8 (CLN8) is a novel candidate gene controlling fat deposition. We investigated its novel function and regulation in avian adipogenesis. Five significant SNPs (the most significant SNP, P-value = 21.37E−12) and a single haplotype were detected in the upstream of CLN8 for subcutaneous fat percentage. Subsequently, luciferase assay demonstrated that 5 linked SNPs in the upstream of the CLN8 gene significantly decreased the transcriptional activity of CLN8. Further, ATAC-seq analysis showed that transcription factor binding sites were identified in a region close to the haplotype. A set of luciferase reporter gene vectors that contained different deletion fragments of the CLN8 promoter were constructed, and the core promoter area of CLN8 was finally identified in the −1,884/−1,207 bp region of the 5′ flanking sequences, which contains adipogenesis-related transcription factors binding sites. Moreover, the over-expression of CLN8 can remarkably facilitate adipocyte differentiation in ICPs. Consistent with these, the global transcriptome profiling and functional analysis of the over-expressed CLN8 in the cell line further revealed that the lipid biosynthetic process during the adipogenesis was significantly enriched. Our results demonstrated that CLN8 is a positive regulator of avian adipocyte differentiation. These findings identify a novel function of CLN8 in adipocyte differentiation, which provides important clues for the further study of the mechanism of avian fat deposition. The online version contains supplementary material available at 10.1186/s40104-023-00864-x.
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影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
影响因子：
2.4
作者：
Deng, M-T;Zhang, F.;Hou, Z-C
通讯作者：
Hou, Z-C
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
4.4
作者：
Lin, Fang-Bin;Zhu, Feng;Hou, Zhuo-Cheng
通讯作者：
Hou, Zhuo-Cheng
影响因子：
3.7
作者：
Abdalla BA;Chen J;Nie Q;Zhang X
通讯作者：
Zhang X