REVISÕES SOBRE GATA-1

Referências retiradas do MedLine:
ARTICLE TITLE: Transcription factors and the regulation of haemopoiesis: lessons from GATA and SCL proteins.
ARTICLE SOURCE: Bioessays (England), Jul 1994, 16(7) p481-8
AUTHOR(S): Bockamp EO; McLaughlin F; Murrell A; Green AR
ABSTRACT: One of the central issues of developmental biology concerns the molecular mechanisms whereby a multipotent cell gives rise to distinct differentiated progeny. Differences between specialised cell types reflect variations in their patterns of gene expression. The regulation of transcription initiation is an important control point for gene expression and it is, therefore, not surprising that transcription factors play a pivotal role in mammalian development and differentiation. Haemopoiesis offers a uniquely tractable system for the study of lineage commitment and differentiation. The importance of transcription factors in the normal regulation of haemopoiesis is underlined by the frequency with which transcription factors are targeted by leukaemogenic mutations. Studies of the function and regulation of haemopoietic transcription factors, especially those expressed in lineage-restricted patterns, should greatly increase our understanding of the molecular control of haemopoiesis. In this review we have focused on insights provided by recent studies of the GATA and SCL proteins.

ARTICLE TITLE: GATA transcription factors: key regulators of hematopoiesis.
ARTICLE SOURCE: Exp Hematol (United States), Feb 1995, 23(2) p99-107
AUTHOR(S): Weiss MJ; Orkin SH

ARTICLE TITLE: Function of PU.1 (Spi-1), C/EBP, and AML1 in early myelopoiesis: regulation of multiple myeloid CSF receptor promoters.
ARTICLE SOURCE: Curr Top Microbiol Immunol (Germany), 1996, 211 p137-47
AUTHOR(S): Zhang DE; Hohaus S; Voso MT; Chen HM; Smith LT; Hetherington CJ; Tenen DG
ABSTRACT: Our studies of the promoters of the myeloid CSF receptors (M, GM, and G) in cell lines have led to the findings that the promoters are small, and are all activated by the PU.1 and C/EBP proteins. To date, we have only found evidence for involvement of C/EBP alpha, although further experiments will be needed to exclude the role of C/EBP beta and C/EBP delta in receptor gene expression. These studies suggest a model of hematopoiesis (Fig. 2) in which the lineage commitment decisions of multipotential cells are made by the alternative patterns of expression of certain transcription factors, which then activate growth factor receptors which allow those cells to respond to the appropriate growth factor to proliferate and survive. For example, expression of GATA-1 activates its own expression, as well as that of the erythropoietin receptor, inducing these cells to be capable of responding to erythropoietin. Similarly, expression of PU.1 activates its own promoter, and turns on the three myeloid CSF receptors (M, GM, and G), pushing these cells along the pathway of myeloid differentiation. C/EBP proteins, particularly C/EBP alpha, are also critical for myeloid receptor promoter function, and may also act via autoregulatory mechanisms. Murine C/EBP alpha has a C/EBP binding site in its own promoter. Human C/EBP alpha autoregulates its own expression in adipocytes by activating the USF transcription factor. Myeloid genes expressed later during differentiation, such as CD11b, are also activated by PU.1, which is expressed at highest levels in mature myeloid cells, but not by C/EBP alpha, which is downregulated in a differentiated murine myeloid cell line. Consistent with this model are the findings that overexpression of PU.1 in erythroid cells blocks erythroid differentiation, leading to erythroleukemia, and overexpression of GATA-1 in a myeloid line blocks myeloid differentiation. While these findings have provided some framework for understanding myeloid gene regulation, there are a number of critical questions to be addressed in the near future: What is the pattern of expression of the C/EBP proteins during the course of myeloid differentiation and activation of human CD34+ cells? What is the effect of targeted disruption and other mutations of the C/EBP and AML1 proteins on myeloid development and receptor expression? What are the interactions among these three different types of factors (ets, basic region-zipper, and Runt domain proteins) to activate the promoters? What is the effect of translocations, mutations, and alterations in expression of these factors, particularly in different forms of AML?