Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter.

Abstract

Transcription of erythroid-expressed genes and normal erythroid development in vivo are dependent on a regulatory protein (GATA-1) that recognizes a consensus GATA motif. GATA-1 expression is itself restricted to erythroid progenitors and to two related hematopoietic lineages, megakaryocytes and mast cells. During cellular maturation the levels of GATA-1 RNA and protein increase progressively. In an effort to delineate mechanisms by which this pivotal transcription factor is itself regulated we have characterized the mouse GATA-1 gene and cis-elements within its promoter. We find that the isolated promoter retains cell specificity exhibited by the intact gene. Full promoter activity requires the presence of proximal CACCC box sequences and an upstream, double GATA motif that binds a single GATA-1 molecule in an asymmetric fashion. Using in vivo footprinting of mouse erythroleukemic cells we detect protein binding in vivo to both cis-elements. On the basis of these findings we propose that a positive feedback loop mediated through GATA-1 serves two complementary functions: maintenance of the differentiated state by locking the promoter into an "on" state, and programming the progressive increase in protein content throughout cellular maturation.

GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells

“…Many transcription factors are thought to play a role in erythropoiesis, such as GATA-1 (Kulessa et al, 1995;Tsai et al, 1991), GATA-2 (Tsai et al, 1994), PU.1 (Hromas et al, 1993;Schuetze et al, 1992Schuetze et al, , 1993 and SCL (Aplan et al, 1992;Begley et al, 1989;Shivdasani and Orkin, 1996). Among these, the role of PU.1 in erythropoiesis is still controversial.…”

end-1 encodes an apparent GATA factor that specifies the endoderm precursor in Caenorhabditis elegans embryos

“…In addition, END-1 might also regulate its own expression, as suggested by the presence of GATA consensus sites upstream of the end-1 coding sequence near other putative regulatory elements. Such autoregulation has been proposed for the mouse and chicken GATA-1 genes (Hannon et al 1991;Tsai et al 1991).…”

Alternative promoters and polyadenylation regulate tissue‐specific expression of Hemogen isoforms during hematopoiesis and spermatogenesis

“…Of interest, GATA-1 is also expressed as distinct mRNA isoforms in blood cells and testis under the control of two alternative promoters (Ito et al, 1993). While GATA-1 expression in hematopoietic tissues is under the control of the combination of the GATA-1 site and three other distinct regulatory elements (Tsai et al, 1991;Ohneda et al, 2002), the regulatory mechanisms for GATA-1 expression in testis remains to be defined. The possibility that a distinct regulatory network regulates HEMGN expression in testis is suggested by the observation that the 5Ј upstream sequence of the HEMGN-t exon 1t contains binding sites for the Sox-5 transcription factor, which is highly expressed in round spermatids (Denny et al, 1992).…”