Dynamic changes in the locus control region of erythroid progenitor cells
demonstrated by polymerase chain reaction
J Yoo, LE Herman, C Li, SB Krantz and D Tuan
Harvard-MIT Division of Health Sciences & Technology, Massachusetts
Institute of Technology, Cambridge, USA.
The locus control region (LCR) far upstream of the human beta-like globin
genes is defined by the preferential chromatin accessibility/DNase I
hypersensitivity of four constituent DNA sites HS4, 3, 2, and 1. In an
attempt to understand the mechanism of LCR function during early stages of
erythropoiesis, a new polymerase chain reaction (PCR) method has been
developed to examine the chromatin structure/DNase I hypersensitivity of
the LCR in progenitor cells logistically available in limited cell numbers.
In erythroid progenitors as well as in multipotent cells with erythroid
potential, hypersensitive sites HS4, 3, 2, and 1 were present and the
chromatin structure of the LCR was accessible. Moreover, the chromatin
structure of the LCR underwent dynamic changes during erythropoiesis. In
early erythroid progenitors, the HS2 site was more accessible than the HS3
site. In more mature erythroid progenitors, HS2 became less accessible than
HS3 and the other sites. The results indicate that the transcriptional
program of the globin genes is encoded, at least in part, in the chromatin
accessibility of the LCR. This globin program was apparently initiated in
multipotent cells and maintained in erythroid progenitors. Furthermore, the
program could be modulated in response to cellular changes accompanying
differentiation of the progenitor cells.
Volume 87,
Issue 6,
pp. 2558-2567,
03/15/1996
Copyright © 1996 by The American Society of Hematology
