Expression of the apolipoprotein E gene in the skin is controlled by a unique downstream enhancer.
A distal enhancer that specifies apolipoprotein E gene expression in the skin was identified and characterized by in situ hybridization in transgenic mice generated with constructs of the human apolipoprotein E/C-I/C-IV/C-II gene cluster. Transgene constructs containing the enhancer expressed high levels of apolipoprotein E mRNA in the germinative cell layer of the sebaceous gland and in epithelial cells of the hair follicle root sheath. Apolipoprotein E mRNA was also detected in basal epithelial cells of the epidermis. Expression of the human apolipoprotein E transgene at these sites was specified by a unique 1.0 kb enhancer domain located 1.7 kb downstream of the apolipoprotein E gene. No transgene expression was detected in skin epithelial cells in transgenic mice when this enhancer was deleted from the apolipoprotein E gene cluster. The enhancer was used to construct a transgene expression vector that faithfully directed a heterologous cDNA to the normal sites of apolipoprotein E gene expression in epithelial cells of the skin.
Grehan
S
S
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141, USA.
Allan
C
C
Tse
E
E
Walker
D
D
Taylor
J M
JM
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D018859:Hair Follicle / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D012627:Sebaceous Glands / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000378:metabolism*
D001057:Apolipoproteins E; D012333:RNA, Messenger