Molecular processes during fat cell development revealed by gene expression profiling and functional annotation.

Molecular processes during fat cell development revealed by gene expression profiling and functional annotation.
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DOI:
10.1186/gb-2005-6-13-r108
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发表时间:
2005
期刊:
影响因子:
12.3
通讯作者:
Trajanoski Z
Trajanoski Z
中科院分区:
生物学1区
文献类型:
--
作者:
Hackl H;Burkard TR;Sturn A;Rubio R;Schleiffer A;Tian S;Quackenbush J;Eisenhaber F;Trajanoski Z

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对在3 T3-L1前脂肪细胞分化过程中发现差异表达的表达序列标签进行深入的生物信息学分析,并将其与从头功能注释和映射到已知途径上相结合,以生成脂肪细胞发育的分子图谱。细胞模型和模式生物的大规模转录谱分析可以鉴定参与脂肪细胞发育的新分子组分。尚未对已鉴定基因产物的序列进行详细表征,也未对总体机制进行研究。我们评估了脂肪细胞发育过程中差异表达基因的表达谱和功能注释可以揭示分子过程的程度。开发了具有超过27,000个元件的小鼠微阵列,并在分化期间监测3 T3-L1细胞(前脂肪细胞)的转录谱。总共对780个差异表达序列标签(EST)进行了深入的生物信息学分析。对395个EST的3 '端非翻译区序列分析表明,71%的差异表达基因可由microRNA调控。脂肪细胞发育的分子图谱,然后构建从头功能注释的序列片段/结构域的基础上的659个蛋白质序列,并随后映射到已知的途径,可能的细胞作用,和亚细胞定位。在36个研究的代谢途径中,有27个关键酶在转录水平上受到调控,通常在这些途径的限速步骤。此外,共表达的基因很少共享一致的转录因子结合位点,并且通常不聚集在相邻的染色体区域,而是广泛分散在整个基因组中。大规模转录谱分析与复杂的生物信息学分析相结合,不仅可以提供特定环境中的新参与者列表,还可以提供对生物过程和分子网络的全局视图。
In-depth bioinformatics analyses of expressed sequence tags found to be differentially expressed during differentiation of 3T3-L1 pre-adipocyte cells were combined with de novo functional annotation and mapping onto known pathways to generate a molecular atlas of fat-cell development. Large-scale transcription profiling of cell models and model organisms can identify novel molecular components involved in fat cell development. Detailed characterization of the sequences of identified gene products has not been done and global mechanisms have not been investigated. We evaluated the extent to which molecular processes can be revealed by expression profiling and functional annotation of genes that are differentially expressed during fat cell development. Mouse microarrays with more than 27,000 elements were developed, and transcriptional profiles of 3T3-L1 cells (pre-adipocyte cells) were monitored during differentiation. In total, 780 differentially expressed expressed sequence tags (ESTs) were subjected to in-depth bioinformatics analyses. The analysis of 3'-untranslated region sequences from 395 ESTs showed that 71% of the differentially expressed genes could be regulated by microRNAs. A molecular atlas of fat cell development was then constructed by de novo functional annotation on a sequence segment/domain-wise basis of 659 protein sequences, and subsequent mapping onto known pathways, possible cellular roles, and subcellular localizations. Key enzymes in 27 out of 36 investigated metabolic pathways were regulated at the transcriptional level, typically at the rate-limiting steps in these pathways. Also, coexpressed genes rarely shared consensus transcription-factor binding sites, and were typically not clustered in adjacent chromosomal regions, but were instead widely dispersed throughout the genome. Large-scale transcription profiling in conjunction with sophisticated bioinformatics analyses can provide not only a list of novel players in a particular setting but also a global view on biological processes and molecular networks.
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期刊: DIFFERENTIATION
影响因子: 2.9
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