Roméo P H
INSERM U91, Hôpital Henri-Mondor, Créteil, France.
C R Seances Soc Biol Fil. 1997;191(1):105-11.
Commitment and differentiation of hematopoietic stem cells are associated with the progressive restriction of cellular proliferation and the progressive expression of a subset of genes encoding the markers of mature cells. These two processes are genetically regulated and, in this paper, I review the expression and function of the GATA family of transcription factors as an example of this genetic regulation. GATA cis-acting elements are found in most of the regulatory regions of T-lymphoid, erythrocytic and megakaryocytic restricted genes. These GATA motifs are recognized by the members of a family of transcriptional regulators: the GATA family. Three members of this family, GATA-1, 2 and 3 are expressed in hematopoietic cells. They are necessary for the erythrocytic and megakaryocytic lineages (GATA-1), for the T-lymphoid lineage (GATA-3), and for the proliferation of uncommitted hematopoietic precursors (GATA-2). GATA-1 displays at least four functions: activation of the erythrocytic and megakaryocytic specific genes, regulation of the epsilon-->gamma globin switch and control of the cell cycle. These two last functions will be discussed to show the multiple facets of GATA-1 in the genetic regulation of hematopoiesis.
造血干细胞的定向分化与细胞增殖的逐步受限以及编码成熟细胞标志物的一组基因的逐步表达相关。这两个过程受基因调控,在本文中,我将以转录因子GATA家族的表达和功能为例,阐述这种基因调控。在大多数T淋巴细胞、红细胞和巨核细胞特异性基因的调控区域中都发现了GATA顺式作用元件。这些GATA基序可被一类转录调节因子识别,即GATA家族。该家族的三个成员,GATA-1、2和3在造血细胞中表达。它们对于红细胞和巨核细胞谱系(GATA-1)、T淋巴细胞谱系(GATA-3)以及未定向造血前体细胞的增殖(GATA-2)是必需的。GATA-1至少具有四种功能:激活红细胞和巨核细胞特异性基因、调控ε-珠蛋白向γ-珠蛋白转换以及控制细胞周期。将讨论后两种功能,以展示GATA-1在造血基因调控中的多方面作用。