Roles of Hematopoietic Transcription Factors GATA-1 and GATA-2 in the Development of Red Blood Cell Lineage

Abstract

The transcription factors GATA-1 and GATA-2 play key roles in gene regulation during erythropoiesis. Gene ablation studies in mouse revealed that GATA-2 is crucial for the maintenance and proliferation of immature hematopoietic progenitors, whereas GATA-1 is essential for the survival of erythroid progenitors as well as the terminal differentiation of erythroid cells. Both GATA-1 and GATA-2 are regulated in a cell-type-specific manner, their expression being strictly controlled during the development and differentiation of erythroid cells. Closer examination revealed a cross-regulatory mechanism by which GATA-1 can control the expression of GATA-2 and vice versa, possibly via essential GATA binding sites in their cis-acting elements. In addition, recent studies identified several human inherited hematopoietic disorders that are caused by mutations in cis-acting GATA binding motifs or mutations in GATA-1 itself.

Overexpression of Ets-1 in human hematopoietic progenitor cells blocks erythroid and promotes megakaryocytic differentiation

“…In erythroid cells a decrease of GATA-2 gene expression was shown to be required for differentiation, 17,19,20 as its overexpression in hematopoietic cells inhibits erythroid maturation. [19][20][21] Conversely, GATA-2 remains expressed at high level during all maturation stages of primary human MK cells, 14 and our unpublished observation. Although the functional contribution of GATA-2 in normal megakaryocyte development remains to be determined, its overexpression in hematopoietic cell lines was shown to induce MK differentiation.…”

“…16,18 Several data suggest that the levels of GATA-2 expression determine in part the fate along megakaryocyte-erythroid differentiation pathway. [19][20][21][22] During erythropoiesis GATA proteins switch from GATA-2, in early progenitors, to GATA-1 in terminally differentiating cells therefore linking GATA-2 downregulation to terminal erythroid maturation. [19][20][21] On the contrary, GATA-2 is expressed at high levels during MK differentiation, 14 suggesting a relevant role of GATA-2 also during terminal thrombopoiesis.…”

“…[19][20][21][22] During erythropoiesis GATA proteins switch from GATA-2, in early progenitors, to GATA-1 in terminally differentiating cells therefore linking GATA-2 downregulation to terminal erythroid maturation. [19][20][21] On the contrary, GATA-2 is expressed at high levels during MK differentiation, 14 suggesting a relevant role of GATA-2 also during terminal thrombopoiesis. 22 However, despite the pivotal role played by GATA-2 during hematopoiesis, the mechanisms controlling its expression are still largely unexplored.…”

Ski can negatively regulates macrophage differentiation through its interaction with PU.1

“…Ski has been proposed to recruit such corepressor complexes to certain DNA-binding proteins Liu et al, 2001). In addition, we recently identified GATA1, a lineage-specific transcription factor essential for erythropoiesis (Ohneda and Yamamoto, 2002), as a target of Ski (Ueki et al, 2004). The mechanism by which Ski blocks GATA1 function is unique, as Ski prevents GATA1 DNA binding.…”

A regulatory SNP in AKAP13 is associated with blood pressure in Koreans

“…Moreover, the minor allele of this SNP was predicted by the TFsearch program to disrupt GATA-3 binding to the AKAP13 promoter. 23 The major allele (A) is the GATA-3 binding site is NNGATARNG (TF score ¼94.7); the underlined nucleotide is changed in the SNP (rs11638762) to T, possibly interrupting its transcriptional regulation. However, we should mention that if three transcripts are not the major transcripts of AKAP13, the effect of rs11638762 on differential expression of AKAP13 might not be influential on the regulation of blood pressure.…”