Regulation of GATA1 levels in erythropoiesis

IUBMB Life. 2020 Jan;72(1):89-105. doi: 10.1002/iub.2192. Epub 2019 Nov 25.


GATA1 is considered as the "master" transcription factor in erythropoiesis. It regulates at the transcriptional level all aspects of erythroid maturation and function, as revealed by gene knockout studies in mice and by genome-wide occupancies in erythroid cells. The GATA1 protein contains two zinc finger domains and an N-terminal transactivation domain. GATA1 translation results in the production of the full-length protein and of a shorter variant (GATA1s) lacking the N-terminal transactivation domain, which is functionally deficient in supporting erythropoiesis. GATA1 protein abundance is highly regulated in erythroid cells at different levels, including transcription, mRNA translation, posttranslational modifications, and protein degradation, in a differentiation-stage-specific manner. Maintaining high GATA1 protein levels is essential in the early stages of erythroid maturation, whereas downregulating GATA1 protein levels is a necessary step in terminal erythroid differentiation. The importance of maintaining proper GATA1 protein homeostasis in erythropoiesis is demonstrated by the fact that both GATA1 loss and its overexpression result in lethal anemia. Importantly, alterations in any of those GATA1 regulatory checkpoints have been recognized as an important cause of hematological disorders such as dyserythropoiesis (with or without thrombocytopenia), β-thalassemia, Diamond-Blackfan anemia, myelodysplasia, or leukemia. In this review, we provide an overview of the multilevel regulation of GATA1 protein homeostasis in erythropoiesis and of its deregulation in hematological disease.

Keywords: GATA1; erythropoiesis; hematological disease; protein homeostasis; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation*
  • Erythroid Cells / cytology*
  • Erythroid Cells / metabolism
  • Erythropoiesis*
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / metabolism*
  • Gene Expression Regulation, Developmental*
  • Humans
  • Signal Transduction


  • GATA1 Transcription Factor