PMID- 19178593
OWN - NLM
STAT- MEDLINE
DCOM- 20090616
LR  - 20211020
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 126
IP  - 3
DP  - 2009 Mar
TI  - Epigenetics and T helper 1 differentiation.
PG  - 299-305
LID - 10.1111/j.1365-2567.2008.03026.x [doi]
AB  - Naive T helper cells differentiate into two subsets, T helper 1 and 2, which 
      either transcribe the Ifng gene and silence the Il4 gene or transcribe the Il4 
      gene and silence the Ifng gene, respectively. This process is an essential 
      feature of the adaptive immune response to a pathogen and the development of 
      long-lasting immunity. The 'histone code' hypothesis proposes that formation of 
      stable epigenetic histone marks at a gene locus that activate or repress 
      transcription is essential for cell fate determinations, such as T helper 1/T 
      helper 2 cell fate decisions. Activation and silencing of the Ifng gene are 
      achieved through the creation of stable epigenetic histone marks spanning a 
      region of genomic DNA over 20 times greater than the gene itself. Key 
      transcription factors that drive the T helper 1 lineage decision, signal 
      transducer and activator 4 (STAT4) and T-box expressed in T cells (T-bet), play 
      direct roles in the formation of activating histone marks at the Ifng locus. 
      Conversely, STAT6 and GATA binding protein 3, transcription factors essential for 
      the T helper 2 cell lineage decision, establish repressive histone marks at the 
      Ifng locus. Functional studies demonstrate that multiple genomic elements up to 
      50 kilobases from Ifng play critical roles in its proper transcriptional 
      regulation. Studies of three-dimensional chromatin conformation indicate that 
      these distal regulatory elements may loop towards Ifng to regulate its 
      transcription. We speculate that these complex mechanisms have evolved to tightly 
      control levels of interferon-gamma production, given that too little or too much 
      production would be very deleterious to the host.
FAU - Aune, Thomas M
AU  - Aune TM
AD  - Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 
      37232-2068, USA. tom.aune@vanderbilt.edu
FAU - Collins, Patrick L
AU  - Collins PL
FAU - Chang, Shaojing
AU  - Chang S
LA  - eng
GR  - R01 AI044924/AI/NIAID NIH HHS/United States
GR  - T32 HL069765/HL/NHLBI NIH HHS/United States
GR  - R01 AI 044924/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20081218
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Chromatin)
RN  - 0 (Histones)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Cell Differentiation/genetics/immunology
MH  - Chromatin/genetics
MH  - Epigenesis, Genetic/*immunology
MH  - Histones/genetics
MH  - Humans
MH  - Interferon-gamma/genetics
MH  - Th1 Cells/*cytology/immunology
PMC - PMC2669810
EDAT- 2009/01/31 09:00
MHDA- 2009/06/17 09:00
PMCR- 2010/03/01
CRDT- 2009/01/31 09:00
PHST- 2009/01/31 09:00 [entrez]
PHST- 2009/01/31 09:00 [pubmed]
PHST- 2009/06/17 09:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - IMM3026 [pii]
AID - 10.1111/j.1365-2567.2008.03026.x [doi]
PST - ppublish
SO  - Immunology. 2009 Mar;126(3):299-305. doi: 10.1111/j.1365-2567.2008.03026.x. Epub 
      2008 Dec 18.