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This is Ann Dean I'm
an investigator at the National
Institutes of Health in the
National Institute of Diabetes
and Digestive and Kidney Diseases.
The hemoglobin genes are
the subject of my research,
in particular, the regulation
of these genes at the level
of chromatin and at the level of
nuclear folding of chromosomes.
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The beta globin locus has long
served as a major paradigm
for studies of eukaryotic gene
regulation and transcription.
In mammals, the alpha and beta
globin loci encode the polypeptides
that form the heteromeric
hemoglobin protein molecule.
Hemoglobin is a
64-kilodalton protein
consisting of four
polypeptide chains.
Two so-called
beta-like globin chains
and two alpha-like globin chains.
In each tetramer, the
four globin chains
are held together by
noncovalent attractions.
The human hemoglobin tetramer
is depicted in the drawing.
The alpha2 beta2 tetramer is
called hemoglobin A, or HbA,
and is the predominant
hemoglobin in adults.
Each chain contains a
heme group, labeled
in the picture, which
coordinates an iron atom.
This moiety gives hemoglobin
its characteristic red color.
Hemoglobin transports oxygen
and CO2 in the bloodstream.
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This scanning electron micrograph
illustrates the classic disc shape
of erythrocytes, or red blood cells.
In adults, during the later stages
of erythroid differentiation,
the genes in both the
alpha and beta globin loci
are expressed at
exceptionally high rates.
This is necessary to
fill the terminally
differentiated erythrocyte
with hemoglobin.
Naturally-occurring mutations
show that coordinated regulation
of the two loci is required,
since imbalance between the alpha
and beta globin chains
leads to anemia.
How the alpha and beta
globin genes achieve
this balanced protein
production is not known.
The iron atom at the
center of each heme group
reversibly binds oxygen in
the alveoli of the lungs,
and releases it in peripheral
tissues in small capillaries.
The oxygen is then used for
the metabolic needs of cells.
In these tissues, CO2 is loaded
for the return trip to the lungs
through the venous system, where
it is exchanged again for oxygen.
