Master Regulatory GATA Transcription Factors: Mechanistic Principles and Emerging Links to Hematologic Malignancies

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2012 Apr 12

PMID 22492510

Citations 115

Authors

Emery H Bresnick

Koichi R Katsumura

Hsiang-Ying Lee

Kirby D Johnson

Archibald S Perkins

Affiliations

Soon will be listed here.

Abstract

Numerous examples exist of how disrupting the actions of physiological regulators of blood cell development yields hematologic malignancies. The master regulator of hematopoietic stem/progenitor cells GATA-2 was cloned almost 20 years ago, and elegant genetic analyses demonstrated its essential function to promote hematopoiesis. While certain GATA-2 target genes are implicated in leukemogenesis, only recently have definitive insights emerged linking GATA-2 to human hematologic pathophysiologies. These pathophysiologies include myelodysplastic syndrome, acute myeloid leukemia and an immunodeficiency syndrome with complex phenotypes including leukemia. As GATA-2 has a pivotal role in the etiology of human cancer, it is instructive to consider mechanisms underlying normal GATA factor function/regulation and how dissecting such mechanisms may reveal unique opportunities for thwarting GATA-2-dependent processes in a therapeutic context. This article highlights GATA factor mechanistic principles, with a heavy emphasis on GATA-1 and GATA-2 functions in the hematopoietic system, and new links between GATA-2 dysregulation and human pathophysiologies.

Citing Articles

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The PRC2 complex epigenetically silences GATA4 to suppress cellular senescence and promote the progression of breast cancer.

Yu W, Lin X, Leng S, Hou Y, Dang Z, Xue S Transl Oncol. 2024; 46:102014.

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Long noncoding RNA GATA2AS influences human erythropoiesis by transcription factor and chromatin landscape modulation.

Liu G, Kim J, Nguyen N, Zhou L, Dean A Blood. 2024; 143(22):2300-2313.

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Pathogenic GATA2 genetic variants utilize an obligate enhancer mechanism to distort a multilineage differentiation program.

Katsumura K, Liu P, Kim J, Mehta C, Bresnick E Proc Natl Acad Sci U S A. 2024; 121(10):e2317147121.

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