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The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression.

ABSTRACT: Human CD11b/CD18 (complement receptor type 3) is a member of the beta 2 integrin subfamily which also includes the heterodimers CD11a/CD18 and CD11c/CD18. The CD11 molecules and the common CD18 are the products of different genes that exhibit distinct though overlapping patterns of tissue- and developmental-specific expression. Whereas expression of CD11b and CD11c is almost exclusively restricted to cells of the myeloid lineage, that of CD11a and CD18 is panleukocytic. To begin to understand the mechanisms by which expression of these gene products is restricted to leukocytes and leukocyte subpopulations and to elucidate the mechanisms by which their expression is coordinated, we have cloned and characterized the promoter region of the CD11b gene. A single transcription initiation site has been identified and the region extending 242 base pairs upstream and 71 base pairs downstream of this site has been shown to be sufficient to direct tissue-, cell-, and development-specific expression in vitro, which mimics that of the CD11b gene in vivo. Within this region there are potential binding sites for transcription factors known to be involved in hematopoietic-specific and phorbol ester-inducible gene expression. Further analysis of this region of the CD11b gene and comparison with the promoters of the CD11a, CD11c, and CD18 genes should lead to significant insights into the molecular mechanisms by which these genes are regulated during hematopoietic development and upon activation.

SUBMITTER: Shelley CS

PROVIDER: S-EPMC52961 | biostudies-other | 1991 Dec

REPOSITORIES: biostudies-other

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The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression.

Shelley C S CS Arnaout M A MA

Proceedings of the National Academy of Sciences of the United States of America 19911201 23

Human CD11b/CD18 (complement receptor type 3) is a member of the beta 2 integrin subfamily which also includes the heterodimers CD11a/CD18 and CD11c/CD18. The CD11 molecules and the common CD18 are the products of different genes that exhibit distinct though overlapping patterns of tissue- and developmental-specific expression. Whereas expression of CD11b and CD11c is almost exclusively restricted to cells of the myeloid lineage, that of CD11a and CD18 is panleukocytic. To begin to understand th ...[more]

PMID: 1683702

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Project description:BACKGROUND: In flowering plants a number of genes have been identified which control the transition from a vegetative to generative phase of life cycle. In bryophytes representing basal lineage of land plants, there is little data regarding the mechanisms that control this transition. Two species from bryophytes - moss Physcomitrella patens and liverwort Marchantia polymorpha are under advanced molecular and genetic research. The goal of our study was to identify genes connected to female gametophyte development and archegonia production in the dioecious liverwort Pellia endiviifolia species B, which is representative of the most basal lineage of the simple thalloid liverworts. RESULTS: The utility of the RDA-cDNA technique allowed us to identify three genes specifically expressed in the female individuals of P.endiviifolia: PenB_CYSP coding for cysteine protease, PenB_MT2 and PenB_MT3 coding for Mysterious Transcripts1 and 2 containing ORFs of 143 and 177 amino acid residues in length, respectively. The exon-intron structure of all three genes has been characterized and pre-mRNA processing was investigated. Interestingly, five mRNA isoforms are produced from the PenB_MT2 gene, which result from alternative splicing within the second and third exon. All observed splicing events take place within the 5'UTR and do not interfere with the coding sequence. All three genes are exclusively expressed in the female individuals, regardless of whether they were cultured in vitro or were collected from a natural habitat. Moreover we observed ten-fold increased transcripts level for all three genes in the archegonial tissue in comparison to the vegetative parts of the same female thalli grown in natural habitat suggesting their connection to archegonia development. CONCLUSIONS: We have identified three genes which are specifically expressed in P.endiviifolia sp B female gametophytes. Moreover, their expression is connected to the female sex-organ differentiation and is developmentally regulated. The contribution of the identified genes may be crucial for successful liverwort sexual reproduction.

Project description:BackgroundCell-specific expression of the gene that encodes brain-derived neurotrophic factor (BDNF) is required for the normal development of peripheral sensory neurons and efficient synaptic transmission in the mature central and peripheral nervous system. The control of BDNF gene expression involves multiple tissue and cell-specific promoters that are differentially regulated. The molecular mechanisms that are responsible for tissue and cell-specific expression of these promoters are still incompletely understood.ResultsThe cloning and analysis of three additional zebrafish (Danio rerio) BDNF gene exons and two associated promoters, is reported. Among them are two exons that generate a novel tripartite mature transcript. The exons were located on the transcription unit, whose overall organization was determined by cloning, Southern blot hybridization and sequence analysis, and compared with the pufferfish (Fugu rubripes) and mammalian BDNF loci, revealing a conserved but more compact organization. Structural and functional analysis of the exons, their adjacent promoters and 5' flanks, showed that they are expressed cell-specifically. The promoter associated with the 5' exon of the tripartite transcript is GC-rich, TATA-less and the 5' flank adjacent to it contains multiple Sp1, Mef2, and AP1 elements. A fusion gene containing the promoter and 1.5 KB of 5' flank is directed exclusively to skeletal muscle of transiently transfected embryos. The second promoter, whose associated 5' exon contains a 25-nucleotide segment of identity with a mammalian BDNF gene exon, was transiently expressed in yolk of the early embryo. RT-PCR analysis of total RNA from whole juvenile fish and adult female skeletal muscle revealed tissue-specific expression of the 5' exons but the novel exon could not be detected even after two rounds of nested PCR.ConclusionThe zebrafish BDNF gene is as complex as the mammalian gene yet much more compact. Its exons are expressed in an independently regulated and cell-specific fashion. An initial structural and functional analysis has shown that the regions controlling zebrafish BDNF gene expression have been cloned and identified. They can now be subjected to detailed molecular and genetic analyses to identify the cellular mechanisms by which the transcription factors that act on these regions control BDNF gene expression.

Project description:BACKGROUND: Alternative promoters usage is an important paradigm in transcriptional control of mammalian gene expression. However, despite the growing interest in alternative promoters and their role in genome diversification, very little is known about how and on what occasions those promoters are differentially regulated. Runx1 transcription factor is a key regulator of early hematopoiesis and a frequent target of chromosomal translocations in acute leukemias. Mice deficient in Runx1 lack definitive hematopoiesis and die in mid-gestation. Expression of Runx1 is regulated by two functionally distinct promoters designated P1 and P2. Differential usage of these two promoters creates diversity in distribution and protein-coding potential of the mRNA transcripts. While the alternative usage of P1 and P2 likely plays an important role in Runx1 biology, very little is known about the function of the P1/P2 switch in mediating tissue and stage specific expression of Runx1 during development. RESULTS: We employed mice bearing a hypomorphic Runx1 allele, with a largely diminished P2 activity, to investigate the biological role of alternative P1/P2 usage. Mice homozygous for the hypomorphic allele developed to term, but died within a few days after birth. During embryogenesis the P1/P2 activity is spatially and temporally modulated. P2 activity is required in early hematopoiesis and when attenuated, development of liver hematopoietic progenitor cells (HPC) was impaired. Early thymus development and thymopoiesis were also abrogated as reflected by thymic hypocellularity and loss of corticomedullary demarcation. Differentiation of CD4/CD8 thymocytes was impaired and their apoptosis was enhanced due to altered expression of T-cell receptors. CONCLUSION: The data delineate the activity of P1 and P2 in embryogenesis and describe previously unknown functions of Runx1. The findings show unequivocally that the role of P1/P2 during development is non redundant and underscore the significance of alternative promoter usage in Runx1 biology.

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The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression.

Publications

The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression.

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