Social regulation of gene expression in human leukocytes

@article{citeulike:1655859, abstract = {BACKGROUND:Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates. RESULTS:DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-kB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways. CONCLUSIONS:These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.}, author = {Cole, Steve and Hawkley, Louise and Arevalo, Jesusa and Sung, Caroline and Rose, Robert and Cacioppo, John }, citeulike-article-id = {1655859}, doi = {http://dx.doi.org/10.1186/gb-2007-8-9-r189}, journal = {Genome Biology}, keywords = {gene\_expression, genetic\_regulatory\_network, socio\_biology}, number = {9}, posted-at = {2007-10-05 09:31:59}, priority = {2}, title = {Social regulation of gene expression in human leukocytes}, url = {http://dx.doi.org/10.1186/gb-2007-8-9-r189}, volume = {8}, year = {2007} }

TY - JOUR ID - citeulike:1655859 L3 - citeulike-article-id:1655859 TI - Social regulation of gene expression in human leukocytes JF - Genome Biology VL - 8 IS - 9 N2 - BACKGROUND:Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates. RESULTS:DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-kB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways. CONCLUSIONS:These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation. KW - gene_expression KW - genetic_regulatory_network KW - socio_biology AU - Cole, Steve AU - Hawkley, Louise AU - Arevalo, Jesusa AU - Sung, Caroline AU - Rose, Robert AU - Cacioppo, John PY - 2007/// UR - http://dx.doi.org/10.1186/gb-2007-8-9-r189 ER -