Abstract
The ZNF202 gene resides in a chromosomal region linked genetically to low high density lipoprotein cholesterol in Utah families. Here we show that the ZNF202 gene product is a transcriptional repressor that binds to elements found predominantly in genes that participate in lipid metabolism. Among its targets are structural components of lipoprotein particles (apolipoproteins AIV, CIII, and E), enzymes involved in lipid processing (lipoprotein lipase, lecithin cholesteryl ester transferase), and several genes involved in processes related to energy metabolism and vascular disease. Based on the linkage and apparent transcriptional function of ZNF202, we propose that ZNF202 is a candidate susceptibility gene for human dyslipidemia.
Highlights
Familial hypoalphalipoproteinemia (HA),1 the most common form of decreased plasma HDL levels, is an independent risk factor for early coronary disease [1]
We show that the ZNF202 gene product is a transcriptional repressor that binds to elements found predominantly in genes that participate in lipid metabolism
Among its targets are structural components of lipoprotein particles, enzymes involved in lipid processing, and several genes involved in processes related to energy metabolism and vascular disease
Summary
The ZNF202 gene resides in a chromosomal region linked genetically to low high density lipoprotein cholesterol in Utah families. In light of the increasingly recognized role of transcription factors in coordinating the transcription of multiple genes in lipid-related pathways [10, 11], we characterized the biochemical function of ZNF202. This analysis reveals that ZNF202 is a transcriptional repressor that binds to the regulatory region of many genes involved in lipid metabolism. ZNF202 joins a growing number of transcription factors acting in metabolic coordination
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