Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein.

Abstract

This paper presents the results of experiments that determine the chromosomal location of the mouse gene encoding CCAAT/enhancer binding protein (C/EBP) and measure its expression as a function of tissue type and temporal period of development in mice and rats. Three alleles of the C/EBP gene were identified according to restriction fragment length polymorphisms. The strain distribution pattern of the three alleles was determined in recombinant inbred mouse strains and compared to that of other mouse genes. These results mapped the gene to a position within 2.5 centimorgans (cM) of the structural gene encoding glucose phosphate isomerase on chromosome 7 of the mouse. The expression pattern of the C/EBP gene was studied by a combination of nucleic acid hybridization and antibody staining assays. High levels of C/EBP mRNA were observed in tissues known to metabolize lipid and cholesterol-related compounds at uncommonly high rates. These included liver, fat, intestine, lung, adrenal gland, and placenta. More detailed analysis of two of these tissues, liver and fat, showed that C/EBP expression was limited to fully differentiated cells. Moreover, analysis of the temporal pattern of expression of C/EBP mRNA in two tissues, liver and intestine, revealed a coordinated induction just prior to birth. These observations raise the possibility that the synthesis of C/EBP may be responsive to humoral factors and that modulation in C/EBP expression might mediate coordinated changes in gene expression that facilitate adaptive challenges met during development or during the fluctuating physiological states of adult life.

A New Preadipocyte Cell Line, AP-18, Established from Adult Mouse Adipose Tissue

“…These transcriptional factors regulating fat cell development were also identified in AP-18 cells. The expression of PPARγ and C/EBPα was not detected in 3T3-L1 cells to prior to their differentiation, and was first detected on day 2 after confluence, and increased levels were observed at day 8, and remained at an unchanged level thereafter (Birkenmeier et al 1989;Cao et al 1991;Tontonoz et al 1994a). However, these two genes were already detected in AP-18 cells on day 0 after confluence, and did not show increased expression levels after that.…”

Myc represses the growth arrest gene gadd45

“…Recently, transient transfection reporter assays demonstrate that in 3T3-L1 cells, ectopic Myc expression can abrogate the C/EBPa mediated activation of gadd45 transcription associated with adipocyte di erentiation (Constance et al, 1996). In addition, Mink et al show ectopic v-Myc can suppress the expression of myelomonocytic speci®c genes by inhibiting both the expression and the function of C/ EBPa transcription factors (Mink et al, 1996) C/EBPa is predominantly expressed in di erentiated cells (Birkenmeier et al, 1989), hence the role of C/EBPa in the G0/G1-associated up-regulation, or Mycmediated repression of gadd45 in cycling cells, remains unclear. Indeed, Myc may repress gadd45 directly by interacting with components of the core transcription complex, indirectly in an enhancer-dependent manner or by a yet unknown mechanism of action.…”

C/EBPαp30 plays transcriptional regulatory roles distinct from C/EBPαp42

“…C/EBPα is highly expressed in a variety of tissues including liver, lung, placenta, and white and brown adipose tissues [1,2]. As a transcription factor, C/EBPα is a central regulator of energy metabolism [3].…”