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Biology 2013, 2(1), 233-283; doi:10.3390/biology2010233

Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes

Inrs-Institut Armand-Frappier, 531, Bd des prairies, Laval, QC H7V 1B7, Canada
Received: 25 December 2012 / Revised: 15 January 2013 / Accepted: 15 January 2013 / Published: 25 January 2013
(This article belongs to the Special Issue Gene Expression and Regulation)
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Abstract

The Natural resistance-associated macrophage protein 1 (Nramp1 or Solute carrier 11 member 1, Slc11a1) transports divalent metals across the membrane of late endosomes and lysosomes in professional phagocytes. Nramp1 represents an ancient eukaryotic cell-autonomous defense whereas the gene duplication that yielded Nramp1 and Nramp2 predated the origin of Sarcopterygians (lobe-finned fishes and tetrapods). SLC11A1 genetic polymorphisms associated with human resistance to tuberculosis consist of potential regulatory variants. Herein, current knowledge of the regulation of SLC11A1 gene expression is reviewed and comprehensive analysis of ENCODE data available for hematopoietic cell-types suggests a hypothesis for the regulation of SLC11A1 expression during myeloid development and phagocyte functional polarization. SLC11A1 is part of a 34.6 kb CTCF-insulated locus scattered with predicted regulatory elements: a 3' enhancer, a large 5' enhancer domain and four elements spread around the transcription start site (TSS), including several C/EBP and PU.1 sites. SLC11A1 locus ends appear mobilized by ETS-related factors early during myelopoiesis; activation of both 5' and 3' enhancers in myelo-monocytic cells correlate with transcription factor binding at the TSS. Characterizing the corresponding cis/trans determinants functionally will establish the mechanisms involved and possibly reveal genetic variation that impacts susceptibility to infectious or immune diseases. View Full-Text
Keywords: natural resistance-associated macrophage protein (Nramp); SLC11A1; regulation of gene expression; myeloid differentiation; genetic variation; HL-60 cells; C/EBPβ; PU.1 natural resistance-associated macrophage protein (Nramp); SLC11A1; regulation of gene expression; myeloid differentiation; genetic variation; HL-60 cells; C/EBPβ; PU.1
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Cellier, M.F.M. Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes. Biology 2013, 2, 233-283.

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