Expression of GATA-1 in a non-hematopoietic cell line induces beta-globin locus control region chromatin structure remodeling and an erythroid pattern of gene expression.
GATA-1 is a hematopoietic transcription factor expressed in erythroid, megakaryocytic, mast cell and eosinophil lineages. It is required for normal erythroid differentiation, the expression of erythroid-specific genes and for the establishment of an active chromatin structure throughout the beta-globin gene locus. GATA-1 is also necessary for the formation and function of the locus control region DNase I hypersensitive site (HS) core elements. To determine whether GATA-1 was sufficient to direct formation of the locus control region (LCR) and an erythroid pattern of gene expression, we expressed GATA-1 in the non-hematopoietic HeLa cell line that does not express other hematopoietic transcription factors but does express GATA-2, GATA-3, and GATA-6. We found that production of the GATA-1 protein resulted in the formation of LCR DNase I HSs 1-4 in their normal locations, and that histones became hyperacetylated within these regulatory elements. Transcription of several erythroid-specific genes was activated in HeLa cells expressing GATA-1, including those coding for alpha-globin, beta-globin, the erythropoietin receptor, the erythroid krüpple-like factor and p45 NF-E2. Despite increased expression of these genes at the mRNA level, their protein products were not detected. These results imply that GATA-1 is sufficient to direct chromatin structure reorganization within the beta-globin LCR and an erythroid pattern of gene expression in the absence of other hematopoietic transcription factors.
Layon
Michael E
ME
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03756, USA.
Ackley
Catherine J
CJ
West
Rachel J
RJ
Lowrey
Christopher H
CH
D000107:Acetylation; D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D003851:Deoxyribonucleases / Q000378:metabolism; D041905:Erythroid Cells / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006410:Hematopoiesis / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D019901:Locus Control Region / Q000235:genetics*; D051379:Mice; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; D006657:Histones; D051741:Kruppel-Like Transcription Factors; D050984:NF-E2 Transcription Factor, p45 Subunit; D012333:RNA, Messenger; C080774:erythroid Kruppel-like factor; D005914:Globins; D003851:Deoxyribonucleases