SAFB1, an RBMX-binding protein, is a newly identified regulator of hepatic SREBP-1c gene.
Sterol regulatory element-binding protein (SREBP)-1c plays a crucial role in the regulation of lipogenic enzymes in the liver. We previously reported that an X-chromosome-linked RNA binding motif (RBMX) regulates the promoter activity of Srebp-1c. However, still unknown was how it regulates the gene expression. To elucidate this mechanism, we screened the cDNA library from mouse liver by yeast two-hybrid assay using RBMX as bait and identified scaffold attachment factor B1 (SAFB1). Immunoprecipitation assay demonstrated binding of SAFB1 to RBMX. Chromatin immunoprecipitation assay showed binding of both SAFB1 and RBMX to the upstream region of Srebp-1c gene. RNA interference of Safb1 reduced the basal and RBMX-induced Srebp-1c promoter activities, resulting in reduced Srebp-1c gene expression. The effect of SAFB1 overexpression on Srebp-1c promoter was found only in the presence of RBMX. These results indicate a major role for SAFB1 in the activation of Srebp-1c through its interaction with RBMX.
Omura
Yasushi
Y
Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Shiga 520-2192, Japan.
Nishio
Yoshihiko
Y
Takemoto
Tadashi
T
Ikeuchi
Chikako
C
Sekine
Osamu
O
Morino
Katsutaro
K
Maeno
Yasuhiro
Y
Obata
Toshiyuki
T
Ugi
Satoshi
S
Maegawa
Hiroshi
H
Kimura
Hiroshi
H
Kashiwagi
Atsunori
A
D000818:Animals; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C518069:RBMX protein, mouse; D016601:RNA-Binding Proteins; D051780:Sterol Regulatory Element Binding Protein 1; C500609:scaffold attachment factor B1, mouse