Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth.
FASEB J
; 24(8): 3083-92, 2010 Aug.
Article
in En
| MEDLINE
| ID: mdl-20371622
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organ Size
/
Down-Regulation
/
Epigenesis, Genetic
/
Gene Regulatory Networks
/
Growth
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2010
Document type:
Article
Affiliation country:
Estados Unidos