Showing papers by "Bruce M. Spiegelman published in 1991"

Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor.

Abstract: The molecular basis for adipocyte-specific gene expression is not known. We have demonstrated that while short (-168) segments of the 5'-flanking sequence of the adipocyte P2 gene containing AP-1- and C/EBP-binding sites can direct expression of a heterologous gene in cultured adipocytes, they cannot support tissue-specific expression in a transgenic mouse. We have therefore analyzed larger segments of the aP2 5'-flanking region by transfection into adipocytes and have found an enhancer at -5.4 kb. This 500-bp enhancer directs expression of the bacterial chloramphenicol acetyltransferase gene in a differentiation-dependent fashion when linked to its own minimal promoter or to an enhancerless SV40 promoter. Moreover, this enhancer stimulates very strong and highly specific expression from the CAT gene in the adipose tissues of transgenic mice. A smaller fragment (190 bpl having enhancer activity in adipocytes was defined and demonstrated to contain a binding site for an abundant nuclear protein. This factor has the binding specificity and several other properties characteristic of the nuclear factor 1 (NF-1} transcription/replication factor family, and mutation of this NF-l-binding site greatly reduces the function of the 500-bp enhancer. These results identify and characterize the first functional enhancer with specificity for adipose cells and also demonstrate that a member(sl of the NF-1 family is involved in adipocyte-specific gene expression.

Adipocyte-specific DNA sequences and use thereof in the production of transgenic animals exhibiting altered fat tissue metabolism

Abstract: Regulatory DNA sequences are provided, which are obtained from the 5' flanking region of genes which are expressed primarily in differentiated adipose tissue These DNA sequences are largely responsible for driving the expression of endogenous genes specifically in adipose tissue in vivo The DNA sequences can be located in a region 5' of the gene, distinct from promoter sequences which provide a site for the initiation of transcription into DNA, or can be located within the region of the promoter itself When operatively linked to a gene encoding a recombinant protein capable of exerting an effect on the metabolism of adipocytes, the DNA sequences of the invention can be used to produce transgenic animals which exhibit altered fat tissue metabolism Depending upon the nature of the gene introduced in the animal or ancestor thereof at an embryonic stage, the transgenic animals are leaner or more obese than non-transgenic animals of the same species

Adipocyte-specific dna sequences and use for the production of transgenic animals exhibiting altered fat metabolism

Abstract: Regulatory DNA sequences are provided, which are obtained from the 5' flanking region of genes which are expressed primarily in differentiated adipose tissue. These DNA sequences are largely responsible for driving the expression of endogenous genes specifically in adipose tissue in vivo. The DNA sequences can be located in a region 5' of the gene, distinct from promoter sequences which provide a site for the initiation of transcription into DNA, or can be located within the region of the promoter itself. When operatively linked to a gene encoding a recombinant protein capable of exerting an effect on the metabolism of adipocytes, the DNA sequences of the invention can be used to produce transgenic animals which exhibit altered fat tissue metabolism. Depending upon the nature of the gene introduced in the animal or ancestor thereof at an embryonic stage, the transgenic animals are leaner or more obese than non-transgenic animals of the same species.