DYNAMIC CHANGES IN THE LOCUS-CONTROL REGION OF ERYTHROID PROGENITOR CELLS DEMONSTRATED BY POLYMERASE CHAIN-REACTION

The locus control region (LCR) far upstream of the human beta-like glo bin 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 st ages of erythropoiesis, a new polymerase chain reaction (PCR) method h as been developed to examine the chromatin structure/DNase I hypersens itivity of the LCR in progenitor cells logistically available in limit ed cell numbers. In erythroid progenitors as well as in multipotent ce lls with erythroid potential, hypersensitive sites HS4, 3, 2, and 1 we re present and the chromatin structure of the LCR was accessible. More over, the chromatin structure of the LCR underwent dynamic changes dur ing erythropoiesis. In early erythroid progenitors, the HS2 site was m ore 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 enco ded, at least in part, in the chromatin accessibility of the LCR. This globin program was apparently initiated in multipotent cells and main tained in erythroid progenitors. Furthermore, the program could be mod ulated in response to cellular changes accompanying differentiation of the progenitor cells. (C) 1996 by The American Society of Hematology.