title: Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth.
abstract: Children grow, but adults do not. The cessation of growth in multiple organs is the end result of a progressive decline in cell proliferation beginning in early life. The mechanisms responsible for this growth deceleration are largely unknown. Using expression microarray and real-time PCR, we identified a common program of gene expression in lung, kidney, and liver during growth deceleration in juvenile rats. Gene ontology analyses and siRNA-mediated knockdown in vitro indicated that many of the down-regulated genes are growth promoting. Down-regulated genes in the program showed declining histone H3K4 trimethylation with age, implicating underlying epigenetic mechanisms. To investigate the physiological processes driving the genetic program, a tryptophan-deficient diet was used to temporarily inhibit juvenile growth in newborn rats for 4 wk. Afterward, microarray analysis showed that the genetic program had been delayed, implying that it is driven by body growth itself rather than age. Taken together, the findings suggest that growth in early life induces progressive down-regulation of a large set of proliferation-stimulating genes, causing organ growth to slow and eventually cease.
authors.affiliation: Developmental Endocrinology Branch, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, CRC, Room 1-3330, 10 Center Dr., MSC-1103, Bethesda, MD 20892-1103, USA. luichunk@mail.nih.gov
authors.forename: Julian C
authors.initials: JC
authors.lastname: Lui
authors.forename: Patricia
authors.initials: P
authors.lastname: Forcinito
authors.forename: Maria
authors.initials: M
authors.lastname: Chang
authors.forename: Weiping
authors.initials: W
authors.lastname: Chen
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Barnes
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baron
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics*; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006128:Growth / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D007668:Kidney; D008099:Liver; D008168:Lung; D008745:Methylation; D009929:Organ Size / Q000235:genetics*; D051381:Rats
chemical_list: D006657:Histones