Gene regulatory networks in lactation: identification of global principles using bioinformatics.
Gene regulatory networks in lactation: identification of global principles using bioinformatics.
复制标题
泌乳中的基因调节网络：使用生物信息学对全球原理的识别。
DOI：
10.1186/1752-0509-1-56
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发表时间：
2007-11-27
影响因子：
--
通讯作者：
German, J Bruce
中科院分区：
文献类型：
--
作者：
Lemay, Danielle G;Neville, Margaret C;Rudolph, Michael C;Pollard, Katherine S;German, J Bruce
妊娠、哺乳和退化期间乳腺发育的分子基础尚不完全清楚。乳腺微阵列数据，细胞定位数据，蛋白质-蛋白质相互作用，和文献挖掘的基因进行了整合和分析，使用统计学，主成分分析，基因本体分析，途径分析，网络分析，以确定全球生物学原则，管理在怀孕，哺乳和退化的分子事件。得出了几个关键原则：（1）近三分之一的转录组波动，以建立，运行和拆卸泌乳装置;（2）编码分泌机制的基因在泌乳前转录;（3）乳蛋白质组的内源性部分的多样性来自少于100个转录本;（4）虽然一些基因在哺乳期开始时有差异转录，但哺乳期转换主要是转录后介导的;（5）泌乳期间物质的分泌不是通过新的基因组功能的上调发生的，但通过广泛的功能转录抑制，如蛋白质降解和细胞-环境通讯;（6）退化开关主要是转录介导的;和（7）在退化早期，转录状态部分恢复到泌乳前状态。一个新的假说分泌减少建议-牛奶产量逐渐下降，因为分泌机制没有转录补充。一个全面的网络蛋白质相互作用在哺乳期间组装和新的调控基因的目标被确定。不到五分之一的转录调节节点在这个哺乳网络已被探索的背景下，哺乳。对未来乳腺癌生物学研究的意义进行了讨论。
The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood. Mammary gland microarray data, cellular localization data, protein-protein interactions, and literature-mined genes were integrated and analyzed using statistics, principal component analysis, gene ontology analysis, pathway analysis, and network analysis to identify global biological principles that govern molecular events during pregnancy, lactation, and involution. Several key principles were derived: (1) nearly a third of the transcriptome fluctuates to build, run, and disassemble the lactation apparatus; (2) genes encoding the secretory machinery are transcribed prior to lactation; (3) the diversity of the endogenous portion of the milk proteome is derived from fewer than 100 transcripts; (4) while some genes are differentially transcribed near the onset of lactation, the lactation switch is primarily post-transcriptionally mediated; (5) the secretion of materials during lactation occurs not by up-regulation of novel genomic functions, but by widespread transcriptional suppression of functions such as protein degradation and cell-environment communication; (6) the involution switch is primarily transcriptionally mediated; and (7) during early involution, the transcriptional state is partially reverted to the pre-lactation state. A new hypothesis for secretory diminution is suggested – milk production gradually declines because the secretory machinery is not transcriptionally replenished. A comprehensive network of protein interactions during lactation is assembled and new regulatory gene targets are identified. Less than one fifth of the transcriptionally regulated nodes in this lactation network have been previously explored in the context of lactation. Implications for future research in mammary and cancer biology are discussed.