RRC ID 43917
Author Rui J, Liu H, Zhu X, Cui Y, Liu X.
Title Epigenetic silencing of CD8 genes by ThPOK-mediated deacetylation during CD4 T cell differentiation.
Journal J Immunol
Abstract Intrathymic CD4/CD8 differentiation is a process that establishes the mutually exclusive expression profiles of the CD4 and CD8 T cell lineage. The RUNX3-mediated silencing of CD4 in CD8 lineage cells has been well documented; however, it is unclear how CD8 is silenced during CD4 lineage differentiation. In this study, we report that, by directly binding the CD8 locus, ThPOK works as a negative regulator that mediates the deacetylation of Cd8 genes and repositions the CD8 alleles close to heterochromatin during the development of the CD4 lineage. The ectopic expression of ThPOK resulted in increased recruitment of histone deacetylases at Cd8 loci; the enhanced deacetylation of Cd8 genes eventually led to impaired Cd8 transcription. In the absence of ThPOK, the enhanced acetylation and transcription of Cd8 genes were observed. The results of these studies showed that Cd8 loci are the direct targets of ThPOK, and, more importantly, they provide new insights into CD8 silencing during CD4 lineage commitment.
Volume 189(3)
Pages 1380-90
Published 2012-8-1
DOI 10.4049/jimmunol.1201077
PII jimmunol.1201077
PMID 22730529
MeSH Acetylation Animals CD4-Positive T-Lymphocytes / cytology CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / metabolism CD8 Antigens / genetics* CD8 Antigens / metabolism Cell Differentiation / genetics* Cell Differentiation / immunology* Cell Line DNA-Binding Proteins / deficiency DNA-Binding Proteins / physiology* Down-Regulation / genetics Down-Regulation / immunology Epigenesis, Genetic / immunology Gene Silencing / immunology* HEK293 Cells Humans Mice Mice, Knockout Mice, Transgenic Suppression, Genetic / immunology Transcription Factors / deficiency Transcription Factors / physiology*
IF 4.718
Times Cited 33
Human and Animal Cells