Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation.
Using data obtained from cDNA representational difference analysis to identify genes induced during neutrophilic differentiation of the 32D clone 3G (32Dcl3G) cells, we isolated cDNA clones for murine and human leucine-rich alpha2-glycoprotein (hLRG), a protein with unknown function purified 25 years ago. Expression of LRG during differentiation of 32Dcl3G cells preceded the expression of lactoferrin and gelatinase but followed myeloperoxidase. LRG transcripts were also detected in human neutrophils and progenitor cells but not in peripheral blood mononuclear cells. Notably, LRG expression was up-regulated during neutrophilic differentiation of human MPD and HL-60 cells but down-regulated during monocytic differentiation of HL-60 cells. The hLRG gene was localized to chromosome 19p13.3, a region to which the genes for several neutrophil granule enzymes also map. The putative promoter region of LRG was found to contain consensus-binding sites for PU.1, C/EBP, STAT, and MZF1. These results suggest that LRG is a novel marker for early neutrophilic granulocyte differentiation.
O'Donnell
Lynn C
LC
Bone Marrow Transplant Program, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University College of Medicine and Public Health, Columbus 43210, USA.
Druhan
Lawrence J
LJ
Avalos
Belinda R
BR
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D018922:HL-60 Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D009195:Peroxidase / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism
D018076:DNA, Complementary; D006023:Glycoproteins; C015246:LRG1 protein, human; D014157:Transcription Factors; D009195:Peroxidase; D007781:Lactoferrin; D018093:Gelatinases