RGD Reference Report - 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.

General

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.
Authors:	Wang, H Liu, F Millette, CF Kilpatrick, DL
Citation:	Wang H, etal., Mol Cell Biol 2002 Dec;22(24):8478-90.
RGD ID:	628485
Pubmed:	PMID:12446768 (View Abstract at PubMed)
PMCID:	PMC139869 (View Article at PubMed Central)
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.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of transcription by RNA polymerase II	acts_upstream_of_or_within	IDA		628485	PMID:12446768	MGI

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
DNA-binding transcription factor activity		TAS		628485		RGD
sequence-specific DNA binding	enables	IDA		628485	PMID:12446768	MGI

Objects Annotated

Genes (Rattus norvegicus)

Srebf2 (sterol regulatory element binding transcription factor 2)

Srebf2_v1 (sterol regulatory element binding factor 2, variant 1)

Objects referenced in this article

Gene	Srebf2	sterol regulatory element binding factor 2	Mus musculus
Gene	Srebf2_v2	sterol regulatory element binding factor 2, variant 2	Rattus norvegicus

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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.