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Differential regulation of H4 histone gene expression in 3T3‐L1 pre‐adipocytes during arrest of proliferation following contact inhibition or differentiation and its modulation by TGFβ 1
Author(s) -
Bortell Rita,
van Wijnen Andre J.,
RamseyEwing Anna L.,
Stein Gary S.,
Stein Janet L.
Publication year - 1992
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240500111
Subject(s) - microbiology and biotechnology , histone , gene expression , modulation (music) , transforming growth factor , gene , differential (mechanical device) , contact inhibition , chemistry , biology , cell growth , biochemistry , philosophy , aerospace engineering , engineering , aesthetics
The aim of this study was to address whether there is a fundamental difference in regulation of histone gene expression in cells that have become quiescent but retain the ability to proliferate, compared with those cells that have differentiated. We compared multiple levels of regulation of histone gene expression during 3T3‐L1 pre‐adipocyte differentiation. Confluent cells induced to differentiate by treatment with insulin, dexamethasone, and isobutylemethylxanthine initially exhibited an increased proliferative response compared with cells given serum alone. This initial differentiation response was associated with a twofold increase in both histone gene transcription and cellular histone mRNA levels, as well as with enhanced sequence‐specific binding of nuclear factors to the proximal cell‐cycle‐regulatory element of the H4 histone promoter. Transforming growth factor β 1 , an inhibitor of 3T3‐L1 differentiation, increased both the percentage of proliferating cells and the cellular levels of histone mRNA when given in addition to serum stimulation, but no enhancement of these parameters was observed upon addition of TGFβ 1 to the differentiation treatment. Interestingly, although TGFβ 1 enhanced binding of nuclear factors to the proximal cell cycle regulatory element of the histone promoter, these protein/DNA interactions were not associated with an increase in histone transcription. Our results are consistent with the down‐regulation of histone gene expression at confluency being controlled primarily at the post‐transcriptional level, in contrast to an increased involvement of transcriptional down‐regulation at the onset of differentiation. © 1992 Wiley‐Liss, Inc.