Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression.
The glucocorticoid receptor regulates transcription through DNA binding as well as through cross-talk with other transcription factors. In hepatocytes, the glucocorticoid receptor is critical for normal postnatal growth. Using hepatocyte-specific and domain-selective mutations in the mouse we show that Stat5 in hepatocytes is essential for normal postnatal growth and that it mediates the growth-promoting effect of the glucocorticoid receptor through a direct interaction involving the N-terminal tetramerization domain of Stat5b. This interaction mediates a selective and unexpectedly extensive part of the transcriptional actions of these molecules since it controls the expression of gene sets involved in growth and sexual maturation.
Engblom
David
D
Division of Molecular Biology of the Cell I, German Cancer Research Center, D-69120 Heidelberg, Germany.
Kornfeld
Jan-Wilhelm
JW
Schwake
Lukas
L
Tronche
Francois
F
Reimann
Andreas
A
Beug
Hartmut
H
Hennighausen
Lothar
L
Moriggl
Richard
R
Schütz
Günther
G
D000818:Animals; D015153:Blotting, Western; D049628:Body Size / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011965:Receptors, Glucocorticoid / Q000378:metabolism* / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012741:Sexual Maturation / Q000235:genetics
D011965:Receptors, Glucocorticoid; D050799:STAT5 Transcription Factor