tailieunhanh - Báo cáo Y học: 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 | Eur. J. Biochem. 269 3607-3618 2002 FEBS 2002 doi REVIEW ARTICLE Transcriptional regulation of erythropoiesis Fine tuning of combinatorial multi-domain elements Chava Perry1 2 and Hermona Soreq1 1 Department of Biological Chemistry The Institute of Life Sciences The Hebrew University of Jerusalem Israel department of Hematology The Tel Aviv Sourasky Medical Center Tel Aviv and Tel Aviv University Israel 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 . 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 .