Cloning and functional characterization of the human fractalkine receptor promoter regions.
We have previously shown that reduced expression of the fractalkine receptor, CX3CR1, is correlated with rapid HIV disease progression and with reduced susceptibility to acute coronary events. In order to elucidate the mechanisms underlying transcriptional regulation of CX3CR1 expression, we structurally and functionally characterized the CX3CR1 gene. It consists of four exons and three introns spanning over 18 kb. Three transcripts are produced by splicing the three untranslated exons with exon 4, which contains the complete open reading frame. The transcript predominantly found in leucocytes corresponds to the splicing of exon 2 with exon 4. Transcripts corresponding to splicing of exons 1 and 4 are less abundant in leucocytes and splicing of exons 3 and 4 are rare longer transcripts. A constitutive promoter activity was found in the regions extending upstream from untranslated exons 1 and 2. Interestingly, exons 1 and 2 enhanced the activity of their respective promoters in a cell-specific manner. These data show that the CX3CR1 gene is controlled by three distinct promoter regions, which are regulated by their respective untranslated exons and that lead to the transcription of three mature messengers. This highly complex regulation may allow versatile and precise expression of CX3CR1 in various cell types.
Garin
Alexandre
A
Laboratoire d'Immunologie Cellulaire et Tissulaire, INSERM U543, Hôpital Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, AP-HP, 75634 Paris cedex 13, France.
Pellet
Philippe
P
Deterre
Philippe
P
Debré
Patrice
P
Combadière
Christophe
C
D017398:Alternative Splicing; D001483:Base Sequence; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics*; D015728:Receptors, HIV / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D000073883:CX3C Chemokine Receptor 1; D018076:DNA, Complementary; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV