GATA1 Activity Governed by Configurations of cis-Acting Elements

Abstract

The transcription factor GATA1 regulates the expression of essential erythroid and megakaryocytic differentiation genes through binding to the DNA consensus sequence WGATAR. The GATA1 protein has four functional domains, including two centrally located zinc-finger domains and two transactivation domains at the N- and C-termini. These functional domains play characteristic roles in the elaborate regulation of diversified GATA1 target genes, each of which exhibits a unique expression profile. Three types of GATA1-related hematological malignancies have been reported. One is a structural mutation in the GATA1 gene, resulting in the production of a short form of GATA1 that lacks the N-terminal transactivation domain and is found in Down syndrome-related acute megakaryocytic leukemia. The other two are cis-acting regulatory mutations affecting expression of the Gata1 gene, which have been shown to cause acute erythroblastic leukemia and myelofibrosis in mice. Therefore, imbalanced gene regulation caused by qualitative and quantitative changes in GATA1 is thought to be involved in specific hematological disease pathogenesis. In the present review, we discuss recent advances in understanding the mechanisms of differential transcriptional regulation by GATA1 during erythroid differentiation, with special reference to the binding kinetics of GATA1 at conformation-specific binding sites.

Long noncoding RNA PCED1B-AS1 promotes erythroid differentiation coordinating with GATA1 and chromatin remodeling

“…In erythroid differentiation, GATA1 is an essential transcription factor involved in a considerable number of target genes that regulate the proliferation, differentiation, and survival of hematopoietic progenitors. 24 Therefore, lncRNA regulated by GATA1 is more likely to play a role in erythropoiesis. To screen for potential GATA1-regulated lncRNAs, we first analyzed the ChIP-seq data from K562 erythroid cells in the ENCODE database and identified 107 lncRNAs with GATA1 binding sites within 2 kb of their genes.…”

Exploring the Leukemogenic Potential of GATA-1S, the Shorter Isoform of GATA-1: Novel Insights into Mechanisms Hampering Respiratory Chain Complex II Activity and Limiting Oxidative Phosphorylation Efficiency

“…Hematopoietic homeostasis is maintained by a refined equilibrium between selfrenewal, proliferation, differentiation and survival of hematopoietic stem cells and their progeny with each process being supported by the balanced expression of several specific genes, regulated by different transcription factors. In this context, the GATA-1 factor plays a key role in regulating the expression of a large set of hematopoietic-related genes [32,61]. Therefore, not surprisingly, its dysregulated expression is emerging as a key factor in malignant hematopoiesis [32,62,63].…”

GATA factor transcriptional activity: Insights from genome‐wide binding profiles

“…[8][9][10][11][12][13][14][15][16] Initially, it was shown that GATA1 binds to a WGATAR sequence motif. However, genome-wide studies of GATA1 chromatin occupancy have revised this original sequence motif and have highlighted the presence of single and dual (tandem or palindromic) GATA1 motifs and composite elements containing a sequence motif for collaborative transcription factors (for a review, see 17 ). GATA1 functions as either an activator or a repressor, depending on the gene context.…”