ORGANIZATION AND EXPRESSION OF GLOBIN GENE LOCI

Project: Research project

Project Details

Description

The goal is to elucidate the molecular events involved in the
developmentally regulated expression of rabbit globin genes. Both direct
biochemical assays and interspecies structural comparisons (with their
evolutionary inferences) are used to achieved this goal. These studies are
helpful in understanding human hemoglobinopathies such as thalassemias and
are essential to the design of potential therapeutic regimens. The
mechanisms discovered for the regulation of the globin multigene family may
also be applicable to other gene families which in a defective form cause a
variety of genetic and developmental diseases.

This proposal is specifically designed to continue the studies of the
structure and expression of rabbit Alpha- and Beta-globin gene families in
the following six projects. (1) The complete linkage map of the Zeta and
Alpha globin genes will be established, the genes and flanking regions
sequenced, and the developmental time of expression determined. (2) The
regulation of Alpha1 gene expression will be studied, and the possible
involvement of GC boxes and a conserved 3' flanking sequence will be tested
by in vitro mutagenesis and expression in transfected cells. (3) The
mechanism of attenuation and termination of transcription will be analyzed
for both Alpha and Beta genes. Our model for transcriptional attenuation
involving stern- and loop formation in the RNA and antisense transcription
will be tested by placing the proposed Beta1 attenuator in viral
transcription units and by appropriate deletion mutagenesis experiments.
The complex transcription unit of Alpha1 will be mapped in detail for a
comparison with Beta 1. (4) Nucleases will be used to dissect aspects of
globin chromatin structure in nucleic from erythroid cells. The sequence
requirements for adopting an unusual DNA conformation sensitive to nuclease
S1 will be determined, and spectroscopic methods will be used to study this
unusual conformation. (5) Structural studies on long L1 repeats will be
completed, and the transcription of both long and short repeats will be
studied in heterologous cells. (6) The sequence of the entire rabbit
Beta-like globin gene cluster (44 kb) will be completed and compared to the
homologous region in humans and mice.
StatusFinished
Effective start/end date12/31/896/30/02

Funding

  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES: $208,094.00
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES: $49,105.00
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES: $214,338.00
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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