Selective induction of CCAAT/enhancer binding protein isoforms occurs during rat liver development.
OBJECTIVE
Recent evidence suggests that CCAAT/enhancer binding protein (C/EBP) transcription factors may regulate hepatocyte terminal differentiation.


METHODS
To explore this possibility, the present study looked for variations in the expression or DNA binding activity of different C/EBP isoforms during rat postnatal liver development and determined which of the C/EBPs were expressed by adult hepatocytes in primary culture.


RESULTS
In intact rats, hepatocyte proliferation is active for 2-3 weeks after birth. During this period of postnatal liver growth, several liver-specific functions emerge and C/EBP alpha, beta, and delta isoforms are induced. Nuclear expression of the 36-kilodalton C/EBP delta protein increases immediately after birth, followed first by increases in the 38-kilodalton C/EBP beta protein expression and then by increases in the 42-kilodalton C/EBP alpha protein expression. Changes in C/EBP DNA binding activity accompany developmental increases in C/EBP proteins. Messenger RNAs of all three C/EBP isoforms are expressed by mature hepatocytes in primary culture.


CONCLUSIONS
Specific C/EBP isoforms are induced differentially during the course of rat postnatal liver development. Young adult rats and cultured adult hepatocytes express all three C/EBP isoforms. These results are consistent with (but do not prove) the theory that variations in C/EBP expression and function help regulate hepatocyte terminal differentiation.
Diehl
A M
AM
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Michaelson
P
P
Yang
S Q
SQ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D007536:Isomerism; D008099:Liver / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D010729:Phosphoenolpyruvate Carboxykinase (GTP)