GATA transcription factors in development and disease

Abstract

The GATA family of transcription factors is of crucial importance during embryonic development, playing complex and widespread roles in cell fate decisions and tissue morphogenesis. GATA proteins are essential for the development of tissues derived from all three germ layers, including the skin, brain, gonads, liver, hematopoietic, cardiovascular and urogenital systems. The crucial activity of GATA factors is underscored by the fact that inactivating mutations in most GATA members lead to embryonic lethality in mouse models and are often associated with developmental diseases in humans. In this Primer, we discuss the unique and redundant functions of GATA proteins in tissue morphogenesis, with an emphasis on their regulation of lineage specification and early organogenesis.

Regulation of GATA1 levels in erythropoiesis

“…This DNA consensus sequence is evolutionarily conserved in fungi, plants, invertebrates, and vertebrates, such as zebrafish, Xenopus , chicken, and mammals, further supporting the notion that GATA family members play important roles in the regulation of crucial cellular processes . In mammals, GATA1, GATA2, and GATA3 have important roles primarily, but not exclusively, within the hematopoietic system and GATA4, GATA5, and GATA6 drive the differentiation of mesoderm and endoderm‐derived tissues, thus regulating diverse developmental processes within the cardiac, gastrointestinal, endocrine, and gonadal systems . The binding of GATA transcription factors to the WGATAR sequence motif depends highly on the C‐terminal zinc finger (C‐ZnF), while the N‐terminal zinc finger (N‐ZnF) domain may bind to sites containing additional canonical, noncanonical (GATC), or palindromic GATA motifs, or may strengthen binding through interaction with other surrounding DNA motifs, mainly in partnership with other transcriptional cofactors .…”

“…GATA1 belongs to the GATA family of transcription factors, which comprises six members: GATA1 to GATA6. The GATA family of transcription factors plays an important role in the regulation of several biological processes, such as embryonic development, cell growth, cell differentiation, and tissue morphogenesis . All members of the GATA family of transcription factors recognize and bind to a specific DNA motif, (A/T)GATA(A/G) (WGATAR), through two highly conserved Cys4‐type zinc finger regions.…”

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

“…GATA2 is also expressed in a variety of non‐hematopoietic tissues (mesenchymal stem cells, endothelium, central nervous system, urogenital organs, lung, prostate, and endometrium) and cancers (lung and prostate cancers) …”

“…[53][54][55][56]68,69 GATA2 is also expressed in a variety of non-hematopoietic tissues (mesenchymal stem cells, endothelium, central nervous system, urogenital organs, lung, prostate, and endometrium) and cancers (lung and prostate cancers). 56,70 GATA2 genome-wide occupancy has been studied in murine and human cell lines and primary cells, including multipotent progenitors, and erythroid, megakaryocytic and mast cells ( Table 2, Table S2). Like GATA1, GATA2 binds mostly to intragenic and intergenic regions.…”

Targeting GATA4 for cardiac repair

“…A network of cardiac transcription factor (TF) controls cardiac gene expression and has a central role in transcriptional regulation during cardiac differentiation and development and the adaptive pathophysiological processes in the adult heart . Evolutionarily conserved cardiac TFs GATA binding protein 4 (GATA4), NK2 homeobox 5 (NKX2‐5), myocyte enhancer factor 2C (MEF2C), heart and neural crest derivatives expressed 2 (HAND2), serum response factor (SRF), and T‐box 5 (TBX5) have been shown to interact with and orchestrate cardiac gene expression during differentiation and development and are also involved in cardiac hypertrophy in a context‐dependent and dynamically evolving manner (Table ).…”