In the laboratory, chromosomal DNA fastens onto material left
over when the cell nucleus is extracted with a high-salt-concentration
solution. (Although this proteinaceous stuff is called the nuclear
matrix, the term was long viewed with suspicion, for lack of direct
evidence that any such matrix exists in the undamaged nucleus.)
In the 1990s Terumi Kohwi-Shigematsu and Yoshinori Kohwi were investigating
these "matrix attachment regions" (MARs). Within MARs,
the two researchers discovered shorter sequences rich in adenine
and thymine bases (A and T). Chloracetaldehyde probes revealed that
here, double-stranded DNA easily unzips into single strands under
the strain imposed by a salty environment. They named their discovery
"base unpairing regions" (BURs).
"We reasoned that if these regions were biologically important,
there must be an important protein associated with them," says
Kohwi-Shigematsu. With BURs as bait, they fished among millions
of clones that express proteins and snagged "special AT-rich
binding protein 1," SATB1.
Found in the precursors of T cells, SATB1 also occurs in other
progenitor cells. Says Kohwi-Shigematsu, "It looks like it
is developmental-state specific." And it's a first: a protein
that forms a structure corresponding to what a real nuclear matrix
DNA sequences known as base unpairing regions (BURs), one strand
consists exclusively of well-mixed A's, T's, and some C's. Here
double-stranded DNA readily separates.
the immune system
The immune system's most important cells include killer T cells,
which attack disease agents directly, and helper T cells that identify
targets and stimulate the body's defenses.
T stands for thymus, the gland where T cells develop from precursor
thymocytes. Before maturing into distinct types, thymocytes show
both of two protein markers, CD4 and CD8. At this double-positive
stage thymocytes grow abundantly, but are soon winnowed into single-positive
CD4 helpers or CD8 killers.
Each type has a chemical arsenal. For example, helper cells secrete
interleukin 2, identifying disease agents and stimulating other
T cells to multiply and attack.
Terumi Kohwi-Shigematsi and her colleagues showed that SATB1 regulates
numerous genes needed for the development of mature T cells, including
the interleukin-2 receptor alpha gene. Specially bred mice without
SATB1 are small and thin and live only three weeks, compared to
a normal two-year lifespan. In thymocytes, lack of gene regulation
by SATB1 wrecks the immune system.