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Silencing and Activation of Embryonic Globin Gene Expression
Author(s) -
GINDER GORDON D.,
SINGAL RAKESH,
LITTLE JANE A.,
DEMPSEY NANCY,
FERRIS RICHARD,
WANG SHOU ZHEN
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10464.x
Subject(s) - gene silencing , gene expression , embryonic stem cell , microbiology and biotechnology , gene , globin , regulation of gene expression , biology , genetics
A bstract : An understanding of the mechanisms that control developmental stage‐specific transcription of globin genes offers the promise of successful therapeutic activation of fetal or embryonic β‐type genes in β‐thalassemia syndromes. A large body of evidence supports the notion of conservation of such mechanisms across vertebrate species and validates the use of pre‐clinical studies of silencing and activation of fetal or embryonic globin genes in animals. Using globin gene transfections into primary avian erythroid cells and cultured murine erythroleukemia cells, we have studied mechanisms involved in stage‐specific embryonic β‐type globin gene silencing and activation. These studies show that 1) methylation of the exact CpG nucleotides that are methylated in normal adult erythroid cells in vivo is capable of blocking transcription of a transfected embryonic globin gene promoter via binding of a methyl DNA binding protein in primary erythroid cells. 2) Activation of embryonic β‐type globin gene transcription in adult erythroid cells by short chain fatty acids is mediated through specific DNA sequences both in the promoter and downstream of the promoter.