Abstract
FOG is a multitype zinc finger protein that is essential for megakaryopoiesis, binds to the amino-terminal finger of GATA-1, and modulates the transcription of GATA-1 target genes. Presently investigated are effects of FOG and GATA-1 on the transcription of the megakaryocytic integrin gene, alpha IIb. In GATA-1-deficient FDCER cells (in the presence of endogenous FOG), ectopically expressed GATA-1 activated transcription 3-10-fold both from alpha IIb templates and the endogenous alpha IIb gene. The increased expression of FOG increased reporter construct transcription 30-fold overall. Unexpectedly, alphaIIb gene transcription also was stimulated efficiently upon the ectopic expression in of FOG per se. This occurred in the absence of any detectable expression of GATA-1 and was observed in multiple independent sublines for both the endogenous alpha IIb gene and transfected constructs yet proved to depend largely upon conserved GATA elements 457 and 55 base pairs upstream from the transcriptional start site. In 293 cells, FOG plus GATA-1 but not FOG alone only moderately stimulated alpha IIb transcription, and no direct interactions of FOG with the alpha IIb promoter were detectable. Thus, FOG acts in concert with GATA-1 to stimulate alpha IIb expression but also can act via a GATA-1-independent route, which is proposed to involve additional hematopoietic-restricted cofactors (possibly GATA-2).
Highlights
Plus Lmo2 [10, 11]
Since FOG is a co-factor for GATA-1 [8] and since functional GATA elements occur within the promoters of most megakaryocytic genes studied to date (20 –25), FOG might act as an obligatory GATA-1 co-factor
To further determine how FOG might affect megakaryocytic gene expression, we presently have investigated whether FOG might regulate the expression of the megakaryocytic integrin subunit, ␣IIb. ␣IIb expression is restricted to megakaryocytes, platelets, and their progenitors [27] and, together with a more broadly expressed subunit 3, forms an integrin receptor that functions in platelet aggregation [28]
Summary
Plus Lmo2 [10, 11]. GATA-1 is a Cys2/Cys2 zinc finger DNAbinding protein that binds preferentially to (A/T)GATA(A/G) elements via its carboxyl-terminal finger domain [12] and is expressed in erythrocytes, megakaryocytes, eosinophils, and mast cells [13,14,15,16]. Residual transcription from p␣IIb545-⌬5Ј⌬3ЈGLuc in these GATA-1-deficient cells was somewhat higher than in FDCER cells, again suggesting that FOG might stimulate m-␣IIb gene expression at least to a limited extent via a GATA element-independent route.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
