Transcriptional regulation of erythropoiesis. Fine tuning of combinatorial multi-domain elements.
Haematopoiesis, the differentiation of haematopoietic stem cells and progenitors into various lineages, involves complex interactions of transcription factors that modulate the expression of downstream genes and mediate proliferation and differentiation signals. Commitment of pluripotent haematopoietic stem cells to the erythroid lineage induces erythropoiesis, the production of red blood cells. This process involves a concerted progression through an erythroid burst forming unit (BFU-E), an erythroid colony forming unit (CFU-E), proerythroblast and an erythroblast. The terminally differentiated erythrocytes, in mammals, lose their nucleus yet function several more months. A well-coordinated cohort of transcription factors regulates the formation, survival, proliferation and differentiation of multipotent progenitor into the erythroid lineage. Here, we discuss broad-spectrum factors essential for self-renewal and/or differentiation of multipotent cells as well as specific factors required for proper erythroid development. These factors may operate solely or as part of transcriptional complexes, and exert activation or repression. Sequence comparisons reveal evolutionarily conserved modular composition for these factors; X-ray crystallography demonstrates that they include multidomain elements (e.g. HLH or zinc finger motifs), consistent with their complex interactions with other proteins. Finally, transfections and genomic studies show that the timing of each factor's expression during the hematopoietic process, the cell lineages affected and the existing combination of other factors determine the erythroid cell fate.
Perry
Chava
C
Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Israel.
Soreq
Hermona
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D050989:GATA2 Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism; D008894:Milk Proteins; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D029867:Xenopus Proteins; D000099232:Proto-Oncogene Protein Spi-1
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; D008667:Metalloproteins; D008894:Milk Proteins; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000099232:Proto-Oncogene Protein Spi-1; C494711:GATA2 protein, human; C443840:KLF17 protein, Xenopus; C501168:KLF3 protein, human; C085117:LMO2 protein, human; C080774:erythroid Kruppel-like factor