Taking advantage of genome-wide approaches we have demonstrated that 5hmC is enriched in T-cell specific active enhancers. We have also shown that 5hmC is enriched in the gene body of lineage-specifying transcription factors (ThPOK, Runx3, Tbx21) at the developmental stage that the expression of these transcription factors is turned on. Collectively, our work has placed 5hmC in the T cell epigenome as a mark that positively correlates with gene expression. We will follow up on these studies to gain mechanistic insight into how TET proteins and 5hmC exert their regulatory functions.
5hmC is enriched in cell-specific active enhancers. Scatter density plot evaluating the coenrichment of 5hmC, H3K4me1, and H3K27ac in all the predicted thymus enhancers. Enhancers that have strong enrichment for H3K27Ac and H3K4me1 are active enhancers. These active enhancers are also decorated with 5hmC. (Tsagaratou, Aijo et al, Proc Natl Acad Sci U S A. 2014 Aug 12; 111(32): E3306–E3315.)
During T cell lineage specification, 5hmC is enriched in key transcription factors at the stage when their expression is turned on. A portrait of intragenic 5hmC is depicted for the Zbtb7b gene, encoding the transcription factor ThPOK that regulates the CD4 lineage. (Tsagaratou, Aijo et al, Proc Natl Acad Sci U S A. 2014 Aug 12; 111(32): E3306–E3315.)
