GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia

Kyle J. Hewitt, Koichi R. Katsumura, Daniel R. Matson, Prithvia Devadas, Nobuyuki Tanimura, Alexander S. Hebert, Joshua J. Coon, Jin Soo Kim, Colin N. Dewey, Sunduz Keles, Siyang Hao, Robert F. Paulson, Emery H. Bresnick

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

An enhancer with amalgamated E-box and GATA motifs (+9.5) controls expression of the regulator of hematopoiesis GATA-2. While similar GATA-2-occupied elements are common in the genome, occupancy does not predict function, and GATA-2-dependent genetic networks are incompletely defined. A “+9.5-like” element resides in an intron of Samd14 (Samd14-Enh) encoding a sterile alpha motif (SAM) domain protein. Deletion of Samd14-Enh in mice strongly decreased Samd14 expression in bone marrow and spleen. Although steady-state hematopoiesis was normal, Samd14-Enh−/− mice died in response to severe anemia. Samd14-Enh stimulated stem cell factor/c-Kit signaling, which promotes erythrocyte regeneration. Anemia activated Samd14-Enh by inducing enhancer components and enhancer chromatin accessibility. Thus, a GATA-2/anemia-regulated enhancer controls expression of an SAM domain protein that confers survival in anemia. We propose that Samd14-Enh and an ensemble of anemia-responsive enhancers are essential for erythrocyte regeneration in stress erythropoiesis, a vital process in pathologies, including β-thalassemia, myelodysplastic syndrome, and viral infection.

Original languageEnglish (US)
Pages (from-to)213-225.e4
JournalDevelopmental cell
Volume42
Issue number3
DOIs
StatePublished - Aug 7 2017

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Keywords

  • GATA-2
  • anemia
  • enhancer
  • erythroid
  • hematopoiesis
  • regeneration

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Hewitt, K. J., Katsumura, K. R., Matson, D. R., Devadas, P., Tanimura, N., Hebert, A. S., Coon, J. J., Kim, J. S., Dewey, C. N., Keles, S., Hao, S., Paulson, R. F., & Bresnick, E. H. (2017). GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia. Developmental cell, 42(3), 213-225.e4. https://doi.org/10.1016/j.devcel.2017.07.009