Sterol regulatory element-binding proteins, designated as SREBP-1 and -2, are synthesized as membrane-bound proteins. They are localized on the endoplasmic reticulum membrane and the nuclear envelope, and activated by a two-step proteolytic processing. The NH2-terminal processed forms are released in the cytosol only when the intracellular cholesterol level is low, and translocated to the nucleus, resulting in the stimulation of transcription of the target genes. The transcriptional regulation requires either Sp1 or NF-Y, which binds its specific DNA-binding site close to the SREBP-binding site. On the contrary, the transcription of the MTP (Microsomal Triglyceride transfer Protein) gene is down-regulated by SREBPs without any participation of either Sp1 or NF-Y.