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Updated: Aug 11, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
Repression of c-kit and its downstream substrates by GATA-1 inhibits cell proliferation during erythroid maturation
Veerendra Munugalavadla1, Louis C Dore, Bai Lin Tan
1Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Cancer Research Institute, 1044 W. Walnut Street, Room 425, Indianapolis, IN 46202, USA. vmunugal@iupui.edu
Abstract:
Stem cell factor (SCF), erythropoietin (Epo), and GATA-1 play an essential role(s) in erythroid development. We examined how these proteins interact functionally in G1E cells, a GATA-1(-) erythroblast line that proliferates in an SCF-dependent fashion and, upon restoration of GATA-1 function, undergoes GATA-1 proliferation arrest and Epo-dependent terminal maturation. We show that SCF-induced cell cycle progression is mediated via activation of the Src kinase/c-Myc pathway. Restoration of GATA-1 activity induced G1 cell cycle arrest coincident with repression of c-Kit and its downstream effectors Vav1, Rac1, and Akt. Sustained expression of each of these individual signaling components inhibited GATA-1-induced cell cycle arrest to various degrees but had no effects on the expression of GATA-1-regulated erythroid maturation markers. Chromatin immunoprecipitation analysis revealed that GATA-1 occupies a defined Kit gene regulatory element in vivo, suggesting a direct mechanism for gene repression. Hence, in addition to its well-established function as an activator of erythroid genes, GATA-1 also participates in a distinct genetic program that inhibits cell proliferation by repressing the expression of multiple components of the c-Kit signaling axis. Our findings reveal a novel aspect of molecular cross talk between essential transcriptional and cytokine signaling components of hematopoietic development.
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