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.