Back to Search
Start Over
Expression of a novel, sterol-insensitive form of sterol regulatory element binding protein 2 (SREBP2) in male germ cells suggests important cell- and stage-specific functions for SREBP targets during spermatogenesis.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2002 Dec; Vol. 22 (24), pp. 8478-90. - Publication Year :
- 2002
-
Abstract
- Cholesterol biosynthesis in somatic cells is controlled at the transcriptional level by a homeostatic feedback pathway involving sterol regulatory element binding proteins (SREBPs). These basic helix-loop-helix (bHLH)-Zip proteins are synthesized as membrane-bound precursors, which are cleaved to form a soluble, transcriptionally active mature SREBP that regulates the promoters for genes involved in lipid synthesis. Homeostasis is conferred by sterol feedback inhibition of this maturation process. Previous work has demonstrated the expression of SREBP target genes in the male germ line, several of which are highly up-regulated during specific developmental stages. However, the role of SREBPs in the control of sterol regulatory element-containing promoters during spermatogenesis has been unclear. In particular, expression of several of these genes in male germ cells appears to be insensitive to sterols, contrary to SREBP-dependent gene regulation in somatic cells. Here, we have characterized a novel isoform of the transcription factor SREBP2, which is highly enriched in rat and mouse spermatogenic cells. This protein, SREBP2gc, is expressed in a stage-dependent fashion as a soluble, constitutively active transcription factor that is not subject to feedback control by sterols. These findings likely explain the apparent sterol-insensitive expression of lipid synthesis genes during spermatogenesis. Expression of a sterol-independent, constitutively active SREBP2gc in the male germ line may have arisen as a means to regulate SREBP target genes in specific developmental stages. This may reflect unique roles for cholesterol synthesis and other functional targets of SREBPs during spermatogenesis.
- Subjects :
- Amino Acid Sequence
Animals
Base Sequence
Brain Chemistry
CCAAT-Enhancer-Binding Proteins
Cloning, Molecular
DNA-Binding Proteins genetics
Helix-Loop-Helix Motifs
Humans
Leucine Zippers
Male
Mice
Models, Biological
Molecular Sequence Data
Promoter Regions, Genetic
Protein Isoforms genetics
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Sequence Alignment
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Sterol Regulatory Element Binding Proteins
Sterols metabolism
Testis cytology
Testis metabolism
Trans-Activators genetics
Transcription Factors genetics
Transcription, Genetic
DNA-Binding Proteins metabolism
Gene Expression Regulation, Developmental
Germ Cells metabolism
Protein Isoforms metabolism
Spermatogenesis physiology
Trans-Activators metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 22
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 12446768
- Full Text :
- https://doi.org/10.1128/MCB.22.24.8478-8490.2002