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

Dev Cell. 2017 Aug 7;42(3):213-225.e4. doi: 10.1016/j.devcel.2017.07.009.


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.

Keywords: GATA-2; anemia; enhancer; erythroid; hematopoiesis; regeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Anemia / metabolism*
  • Animals
  • Cell Proliferation
  • Cell Survival
  • Enhancer Elements, Genetic*
  • Erythrocytes / cytology
  • Erythrocytes / metabolism*
  • Erythropoiesis*
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism*
  • Mice
  • Proteins / genetics*
  • Proteins / metabolism
  • Transcriptional Activation


  • GATA Transcription Factors
  • Proteins
  • Samd14 protein, mouse