TY - JOUR
T1 - Dynamic changes in the locus control region of erythroid progenitor cells demonstrated by polymerase chain reaction
AU - Yoo, Ji
AU - Herman, Lee E.
AU - Li, Chunhua
AU - Krantz, Sanford B.
AU - Tuan Lo, Dorothy
PY - 1996/3/15
Y1 - 1996/3/15
N2 - The locus control region (LCR) far upstream of the human β-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.
AB - The locus control region (LCR) far upstream of the human β-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.
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U2 - 10.1182/blood.v87.6.2558.bloodjournal8762558
DO - 10.1182/blood.v87.6.2558.bloodjournal8762558
M3 - Article
C2 - 8630423
AN - SCOPUS:0029986333
SN - 0006-4971
VL - 87
SP - 2558
EP - 2567
JO - Blood
JF - Blood
IS - 6
ER -