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.
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Authors | 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 |
Journal | Developmental cell
(Dev Cell)
Vol. 42
Issue 3
Pg. 213-225.e4
(08 07 2017)
ISSN: 1878-1551 [Electronic] United States |
PMID | 28787589
(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.)
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Copyright | Copyright © 2017 Elsevier Inc. All rights reserved. |
Chemical References |
- GATA Transcription Factors
- Proteins
- Samd14 protein, mouse
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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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