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Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene.

ABSTRACT: Human CD11a/CD18 is a noncovalently associated heterodimeric receptor expressed exclusively on the surface of lymphocytes and myeloid cells. To begin to understand the mechanisms that direct the expression of the genes encoding this receptor, we have cloned and characterized the promoter region of the CD11a gene and localized cis-acting elements involved in its expression in lymphoid and myeloid cells. One such element is the "LYM" box, which interacts with two sets of DNA-binding activities, one primarily expressed in lymphocytes and preerythroid cells and the other expressed predominantly in myeloid cells. A second element required for expression of the CD11a gene contains the "GAGA" sequence RRRGAGGAAG (R indicates a purine), which interacts with the DNA-binding activities MS-1 and MS-2. MS-1 is expressed exclusively in myeloid cells and probably represents a member of the Ets family of transcription activators. MS-2 is present in epithelial, preerythroid, and lymphoid cells but is only detected in myeloid cells after differentiation. MS-2 also binds to a second element within the CD11a promoter and homologous elements present in the promoter regions of the CD11b and CD43 genes. Since MS-2 interacts with a number of different gene promoters and is developmentally regulated in myeloid cells, it may play a major role in regulating myeloid gene expression.

SUBMITTER: Shelley CS

PROVIDER: S-EPMC46717 | biostudies-other | 1993 Jun

REPOSITORIES: biostudies-other

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Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene.

Shelley C S CS Farokhzad O C OC Arnaout M A MA

Proceedings of the National Academy of Sciences of the United States of America 19930601 11

Human CD11a/CD18 is a noncovalently associated heterodimeric receptor expressed exclusively on the surface of lymphocytes and myeloid cells. To begin to understand the mechanisms that direct the expression of the genes encoding this receptor, we have cloned and characterized the promoter region of the CD11a gene and localized cis-acting elements involved in its expression in lymphoid and myeloid cells. One such element is the "LYM" box, which interacts with two sets of DNA-binding activities, on ...[more]

PMID: 8099450

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Project description:BackgroundThe sporulation of aerial hyphae of Streptomyces coelicolor is a complex developmental process. Only a limited number of the genes involved in this intriguing morphological differentiation programme are known, including some key regulatory genes. The aim of this study was to expand our knowledge of the gene repertoire involved in S. coelicolor sporulation.ResultsWe report a DNA microarray-based investigation of developmentally controlled gene expression in S. coelicolor. By comparing global transcription patterns of the wild-type parent and two mutants lacking key regulators of aerial hyphal sporulation, we found a total of 114 genes that had significantly different expression in at least one of the two mutants compared to the wild-type during sporulation. A whiA mutant showed the largest effects on gene expression, while only a few genes were specifically affected by whiH mutation. Seven new sporulation loci were investigated in more detail with respect to expression patterns and mutant phenotypes. These included SCO7449-7451 that affect spore pigment biogenesis; SCO1773-1774 that encode an L-alanine dehydrogenase and a regulator-like protein and are required for maturation of spores; SCO3857 that encodes a protein highly similar to a nosiheptide resistance regulator and affects spore maturation; and four additional loci (SCO4421, SCO4157, SCO0934, SCO1195) that show developmental regulation but no overt mutant phenotype. Furthermore, we describe a new promoter-probe vector that takes advantage of the red fluorescent protein mCherry as a reporter of cell type-specific promoter activity.ConclusionAerial hyphal sporulation in S. coelicolor is a technically challenging process for global transcriptomic investigations since it occurs only as a small fraction of the colony biomass and is not highly synchronized. Here we show that by comparing a wild-type to mutants lacking regulators that are specifically affecting processes in aerial hypha, it is possible to identify previously unknown genes with important roles in sporulation. The transcriptomic data reported here should also serve as a basis for identification of further developmentally important genes in future functional studies.

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Dataset Information

Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene.

Publications

Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene.

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