Mapping the trancriptional activation status of SREBP1

FERNÁNDEZ ALVAREZ, ANA JULIA; ALVAREZ, MARÍA SOLEDAD; CASADO PINNA, MARTA

Goteborg

Congreso; 35th FEBS Congress; 2010

Federation of European Bichemical Societies (FEBS)

Cholesterol and lipids uptake, biosynthesis and methabolism are strictly regulated by feedback and feed-forward pathways in organisms all along the evolution. Sterol regulatory element-binding proteins (SREBPs) have a central role on the regulation of enzymes implicated in lipid catabolism and de novo biogenesis.  The SREBP family of transcription factors consists of three proteins, SREBP1a and SREBP1c, produced by, and SREBP2.  SREBP1a and 1c are produced by alternative splicing from a single gene. These proteins differ in their target specificity and they also have a differential tissue distribution. Indeed, the expression of each transcript differs between normal tissue and immortalized cell lines. SREBP1c is transcriptional and post-transcriptional regulated by the nutritional status, particularly by insulin, and alterations in the activity of this isoform are implicated in obesity dislipidemia, methabolic syndrome and type 2 diabetes. Transcription factors implicated in SREBP regulation includes SREBP itself, Sp1, NF-Y and LXR-RXR heterodimers. However, the nutritional and tissue specific regulation of the expression of this isoform seems to involve more than a transcriptional factor mechanism.  SREBP1a is regulated by SP1 and Egr1 at the transcriptional level. It not yet clear the physiologic relevance of this isoform.We aim to study the implication of co-regulatory factors and epigenetic events on the regulation of SREBP1 and their relevance on liver and adipose tissue phisiopatology. We performed chromatin inmunoprecipitation assays to determine the activation status of the SREBP1a and SREBP1c promoters in different tissues and cell lines and the transcriptional machinery necessary for the promoters activity.