Gene regulatory networks in lactation: identification of global principles using bioinformatics
Open Access
- 27 November 2007
- journal article
- research article
- Published by Springer Nature in BMC Systems Biology
- Vol. 1 (1) , 56
- https://doi.org/10.1186/1752-0509-1-56
Abstract
Background: The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood. Results: 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. Conclusion: 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.Keywords
This publication has 45 references indexed in Scilit:
- The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-xThe Journal of cell biology, 2007
- Analyzing gene expression data in terms of gene sets: methodological issuesBioinformatics, 2007
- Roles of the Innate Immune System in Mammary Gland Remodeling During InvolutionJournal of Mammary Gland Biology and Neoplasia, 2007
- Mammary epithelial cell: Influence of extracellular matrix composition and organization during development and tumorigenesisThe International Journal of Biochemistry & Cell Biology, 2007
- Ensembl 2007Nucleic Acids Research, 2006
- The Universal Protein Resource (UniProt)Nucleic Acids Research, 2006
- Global properties of biological networksDrug Discovery Today, 2005
- A novel function for Sam68: Enhancement of HIV-1 RNA 3′ end processingRNA, 2004
- Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactationJournal of Lipid Research, 2003
- Prolactin-mediated transcriptional and post-transcriptional control of casein gene expressionCell, 1979