ORGANIZATION AND EXPRESSION OF GLOBIN GENE LOCI

Project: Research project

Project Details

Description

The long term goal of this project is to understand the molecular basis of
globin gene switching in rabbit development. This project relates to the
human diseases Alpha- and Beta-thalassemia, which result from impaired
expression of Alpha- or Beta-globin, and to sicklecell anemia and some
other hemoglobinopathies which may be cured or alleviated by switching
fetal or embryonic globins back on in adult life. In a larger context,
this project addresses fundamental questions about gene regulation in
development, which could provide new insights into the many intractable
diseases that can be described as aberrations in development, e.g. muscular
dystrophy, cystic fibrosis, and diabetes. Our specific aims are to: 1) compare the known rabbit Beta-globin gene
sequences with those from other mammals to test a model for mammalian
globin evolution, 2) determine the transcription unit for the adult
Beta-globin gene, 3) examine aspects of chromatin structure that could be
responsible for the transcriptional control of the Beta-globin family by
cloning the genes into mouse cells via a bovine papilloma virus (BPV)
episome to amplify the signals from active genes and aid in purification of
a minichromosome, 4) measure the stability of the embryonic Beta-globin
mRNAs in the BPV-globin recombinant clones, 5) examine the efficiency of
each of the genes in an in vitro transcription system with and without
reconstitution into chromatin, and 6) test for gene-specific binding
proteins in erythroid nuclei. Other projects are to 7) isolate and
characterize the rabbit Alpha-like globin gene family and 8) complete the
characterization of a repeated sequence family in rabbits and test for
developmental regulation.
StatusFinished
Effective start/end date12/1/8011/30/86

Funding

  • National Institutes of Health

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