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Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.

Abstract Natural killer cells belong to the family of innate lymphoid cells comprising the frontline defense against infected and transformed cells. Development and activation of natural killer cells is highly dependent on interleukin-15 signaling. However, very little is known about the transcription program driving this process. The transcription factor Runx3 is highly expressed in natural killer cells, but its function in these cells is largely unknown. We show that loss of Runx3 impaired interleukin-15-dependent accumulation of mature natural killer cells in vivo and under culture conditions and pregnant Runx3(-/-) mice completely lack the unique population of interleukin-15-dependent uterine natural killer cells. Combined chromatin immunoprecipitation sequencing and differential gene expression analysis of wild-type versus Runx3-deficient in vivo activated splenic natural killer cells revealed that Runx3 cooperates with ETS and T-box transcription factors to drive the interleukin-15-mediated transcription program during activation of these cells. Runx3 functions as a nuclear regulator during interleukin-15-dependent activation of natural killer cells by regulating the expression of genes involved in proliferation, maturation, and migration. Similar studies with additional transcription factors will allow the construction of a more detailed transcriptional network that controls natural killer cell development and function.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title molecular and cellular biology
Publication Year Start




PMID- 24421391
OWN - NLM
STAT- MEDLINE
DCOM- 20140424
LR  - 20150515
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 34
IP  - 6
DP  - 2014 Mar
TI  - Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell
      activation.
PG  - 1158-69
LID - 10.1128/MCB.01202-13 [doi]
AB  - Natural killer cells belong to the family of innate lymphoid cells comprising the
      frontline defense against infected and transformed cells. Development and
      activation of natural killer cells is highly dependent on interleukin-15
      signaling. However, very little is known about the transcription program driving 
      this process. The transcription factor Runx3 is highly expressed in natural
      killer cells, but its function in these cells is largely unknown. We show that
      loss of Runx3 impaired interleukin-15-dependent accumulation of mature natural
      killer cells in vivo and under culture conditions and pregnant Runx3(-/-) mice
      completely lack the unique population of interleukin-15-dependent uterine natural
      killer cells. Combined chromatin immunoprecipitation sequencing and differential 
      gene expression analysis of wild-type versus Runx3-deficient in vivo activated
      splenic natural killer cells revealed that Runx3 cooperates with ETS and T-box
      transcription factors to drive the interleukin-15-mediated transcription program 
      during activation of these cells. Runx3 functions as a nuclear regulator during
      interleukin-15-dependent activation of natural killer cells by regulating the
      expression of genes involved in proliferation, maturation, and migration. Similar
      studies with additional transcription factors will allow the construction of a
      more detailed transcriptional network that controls natural killer cell
      development and function.
FAU - Levanon, Ditsa
AU  - Levanon D
AD  - Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
FAU - Negreanu, Varda
AU  - Negreanu V
FAU - Lotem, Joseph
AU  - Lotem J
FAU - Bone, Karen Rae
AU  - Bone KR
FAU - Brenner, Ori
AU  - Brenner O
FAU - Leshkowitz, Dena
AU  - Leshkowitz D
FAU - Groner, Yoram
AU  - Groner Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140113
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Core Binding Factor Alpha 3 Subunit)
RN  - 0 (Interleukin-15)
RN  - 0 (Interleukin-2)
RN  - 0 (Runx3 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 124148-04-5 (Eimeria tenella sporozoite antigen)
SB  - IM
MH  - Animals
MH  - Antigens, Protozoan/genetics/metabolism
MH  - Cell Movement/genetics
MH  - Cell Proliferation
MH  - Core Binding Factor Alpha 3 Subunit/*genetics/metabolism
MH  - Female
MH  - Interleukin-15/*genetics/metabolism
MH  - Interleukin-2/genetics/metabolism
MH  - Killer Cells, Natural/*metabolism
MH  - Lymphocyte Activation/*genetics
MH  - Mice
MH  - Promoter Regions, Genetic/genetics
MH  - Transcription Factors/*genetics/metabolism
MH  - Transcription, Genetic/genetics
PMC - PMC3958033
EDAT- 2014/01/15 06:00
MHDA- 2014/04/25 06:00
CRDT- 2014/01/15 06:00
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/04/25 06:00 [medline]
AID - MCB.01202-13 [pii]
AID - 10.1128/MCB.01202-13 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2014 Mar;34(6):1158-69. doi: 10.1128/MCB.01202-13. Epub 2014 Jan
      13.