Autoregulation of the human C/EBP{alpha} gene by stimulation of upstream stimulatory factor binding
- Baylor College of Medicine, Houston, TX (United States)
- Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
The human C/EBP{alpha} gene promoter shares significant sequence homology with that of the mouse but has a different mechanism of autoregulation. Activation of the murine promoter by direct binding of C/EBP{alpha} to a site within 200 bp of the transcriptional start was shown to elevate activity by approximately threefold. Unlike its murine counterpart, the human C/EBP{alpha} gene promoter does not contain a cis element that binds the C/EBP{alpha} protein. Neither C/EBP{alpha} nor C/EBP{beta} (NF-Il-6) binds the human C/EBP{alpha} promoter within 437 bp. However, cotransfection studies show that C/EBP{alpha} stimulates transcription of a reporter gene driven by 437 bp of the C/EBP{alpha} promoter. Our studies show that the human C/EBP{alpha} protein stimulates USF to bind to a USF consensus element within C/EBP{alpha} promoter and activates it by two- to threefold. We propose that the human gene employs the ubiquitously expressed DNA-binding protein factor USF to carry out autoregulation. Autoregulation of the human C/EBP{alpha} promoter was abolished by deletion of the USF binding site, CACGTG. Expression of human C/EBP{beta} following transfection did not stimulate USF binding. These studies suggest a mechanism whereby tissue-specific autoregulation can be achieved via a trans-acting factor that is expressed in all cell types. Thus, direct binding of the C/EBP{alpha} protein to the promoter of the C/EBP{alpha} gene is not required for autoregulation. 36 refs., 11 figs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 75504
- Journal Information:
- Molecular and Cellular Biology, Journal Name: Molecular and Cellular Biology Journal Issue: 3 Vol. 15; ISSN 0270-7306; ISSN MCEBD4
- Country of Publication:
- United States
- Language:
- English
Similar Records
Visualization by BiFC of different C/EBP{beta} dimers and their interaction with HP1{alpha} reveals a differential subnuclear distribution of complexes in living cells
Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression