PMID- 28467369
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2079-7737 (Print)
IS  - 2079-7737 (Electronic)
IS  - 2079-7737 (Linking)
VI  - 6
IP  - 2
DP  - 2017 May 3
TI  - Developmental Control of NRAMP1 (SLC11A1) Expression in Professional Phagocytes.
LID - 10.3390/biology6020028 [doi]
LID - 28
AB  - NRAMP1 (SLC11A1) is a professional phagocyte membrane importer of divalent metals 
      that contributes to iron recycling at homeostasis and to nutritional immunity 
      against infection. Analyses of data generated by several consortia and additional 
      studies were integrated to hypothesize mechanisms restricting NRAMP1 expression 
      to mature phagocytes. Results from various epigenetic and transcriptomic 
      approaches were collected for mesodermal and hematopoietic cell types and 
      compiled for combined analysis with results of genetic studies associating single 
      nucleotide polymorphisms (SNPs) with variations in NRAMP1 expression (eQTLs). 
      Analyses establish that NRAMP1 is part of an autonomous topologically associated 
      domain delimited by ubiquitous CCCTC-binding factor (CTCF) sites. NRAMP1 locus 
      contains five regulatory regions: a predicted super-enhancer (S-E) key to 
      phagocyte-specific expression; the proximal promoter; two intronic areas, 
      including 3' inhibitory elements that restrict expression during development; and 
      a block of upstream sites possibly extending the S-E domain. Also the downstream 
      region adjacent to the 3' CTCF locus boundary may regulate expression during 
      hematopoiesis. Mobilization of the locus 14 predicted transcriptional regulatory 
      elements occurs in three steps, beginning with hematopoiesis; at the onset of 
      myelopoiesis and through myelo-monocytic differentiation. Basal expression level 
      in mature phagocytes is further influenced by genetic variation, tissue 
      environment, and in response to infections that induce various epigenetic 
      memories depending on microorganism nature. Constitutively associated 
      transcription factors (TFs) include CCAAT enhancer binding protein beta (C/EBPb), 
      purine rich DNA binding protein (PU.1), early growth response 2 (EGR2) and signal 
      transducer and activator of transcription 1 (STAT1) while hypoxia-inducible 
      factors (HIFs) and interferon regulatory factor 1 (IRF1) may stimulate iron 
      acquisition in pro-inflammatory conditions. Mouse orthologous locus is generally 
      conserved; chromatin patterns typify a de novo myelo-monocytic gene whose 
      expression is tightly controlled by TFs Pu.1, C/ebps and Irf8; Irf3 and nuclear 
      factor NF-kappa-B p 65 subunit (RelA) regulate expression in inflammatory 
      conditions. Functional differences in the determinants identified at these 
      orthologous loci imply that species-specific mechanisms control gene expression.
FAU - Cellier, Mathieu F M
AU  - Cellier MFM
AD  - Inrs-Institut Armand-Frappier, 531, Bd des prairies, Laval, QC H7V 1B7, Canada. 
      mathieu.cellier@iaf.inrs.ca.
LA  - eng
PT  - Journal Article
DEP - 20170503
PL  - Switzerland
TA  - Biology (Basel)
JT  - Biology
JID - 101587988
PMC - PMC5485475
OTO - NOTNLM
OT  - epigenetics
OT  - expression quantitative trait locus (eQTL)
OT  - gene expression
OT  - hematopoiesis
OT  - natural resistance-associated macrophage protein (NRAMP)
OT  - professional phagocytes
OT  - single nucleotide polymorphism
OT  - solute carrier family 11 (SLC11)
OT  - transcription factor
COIS- The author declares no conflict of interest.
EDAT- 2017/05/04 06:00
MHDA- 2017/05/04 06:01
PMCR- 2017/06/01
CRDT- 2017/05/04 06:00
PHST- 2017/01/20 00:00 [received]
PHST- 2017/04/25 00:00 [revised]
PHST- 2017/04/25 00:00 [accepted]
PHST- 2017/05/04 06:00 [entrez]
PHST- 2017/05/04 06:00 [pubmed]
PHST- 2017/05/04 06:01 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - biology6020028 [pii]
AID - biology-06-00028 [pii]
AID - 10.3390/biology6020028 [doi]
PST - epublish
SO  - Biology (Basel). 2017 May 3;6(2):28. doi: 10.3390/biology6020028.