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

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.
AuthorsKyle 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
JournalDevelopmental cell (Dev Cell) Vol. 42 Issue 3 Pg. 213-225.e4 (08 07 2017) ISSN: 1878-1551 [Electronic] United States
PMID28787589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2017 Elsevier Inc. All rights reserved.
Chemical References
  • GATA Transcription Factors
  • Proteins
  • Samd14 protein, mouse
Topics
  • Amino Acid Motifs
  • Anemia (metabolism)
  • Animals
  • Cell Proliferation
  • Cell Survival
  • Enhancer Elements, Genetic
  • Erythrocytes (cytology, metabolism)
  • Erythropoiesis
  • GATA Transcription Factors (genetics, metabolism)
  • Mice
  • Proteins (genetics, metabolism)
  • Transcriptional Activation

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