Towards defining the nuclear proteome

Direct evidence is reported for 2,568 mammalian proteins within the nuclear proteome, consisting of at least 14% of the entire proteome

Conserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimuli

Conserved temporal precedence between IEGs (light blue nodes) and other protein-coding genes (green nodes) is shown by directed edges. Genes annotated with the GO term 'response to endoplasmic reticulum stress' (GO:003497) have a red rectangle around the gene name; red squares indicate genes with CAGE clusters enriched for XBP1 transcription factor binding sites

Transcriptional network dynamics in macrophage activation

AbstractTranscriptional regulatory networks govern cell differentiation and the cellular response to external stimuli. However, mammalian model systems have not yet been accessible for network analysis. Here, we present a genome-wide network analysis of the transcriptional regulation underlying the mouse macrophage response to bacterial lipopolysaccharide (LPS). Key to uncovering the network structure is our combination of time-series cap analysis of gene expression with in silico prediction of transcription factor binding sites. By integrating microarray and qPCR time-series expression data with a promoter analysis, we find dynamic subnetworks that describe how signaling pathways change dynamically during the progress of the macrophage LPS response, thus defining regulatory modules characteristic of the inflammatory response. In particular, our integrative analysis enabled us to suggest novel roles for the transcription factors ATF-3 and NRF-2 during the inflammatory response. We believe that our system approach presented here is applicable to understanding cellular differentiation in higher eukaryotes

Flowchart describing experimental subcellular localization data acquisition

Experimental data were generated by expressing proteins in HeLa cells and determining their subcellular localization. Proteins that localized to the cytoplasm in HeLa cells were then expressed in MCF7 cells. Proteins reported to localize to the nucleus in the LOCATE database were also included in this dataset. Ultimately, all nuclear proteins were combined, resulting in a set of 1,529 proteins.<p><b>Copyright information:</b></p><p>Taken from "Towards defining the nuclear proteome"</p><p>http://genomebiology.com/2008/9/1/R15</p><p>Genome Biology 2008;9(1):R15-R15.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2395251.</p><p></p