Fig. 3. Roles of H3K9 methyltransferases in T cell lineage determination.

The well-characterized differentiation steps from haematopoietic stem cells (HSCs) into terminally differentiated T helper cells (T helper 1 (T_H1) cells, T_H2 cells, T follicular helper (T_FH) cells and T_H17 cells) are shown. The effects of deletion of SUV39H1 and/or SUV39H2, SETDB1 or G9A are listed. Although not shown, histone H3 Lys9 (H3K9) methyltransferases also have a role in the maturation of B cell progenitors (pro-B cells). In this case, the loss of SETDB1 leads to derepression of both specific endogenous retroviruses (ERVs)^69,217 and non-lineage-specific genes, including genes specific to innate immunity⁶⁹. The selection of genes and repeats that are derepressed likely depends on the variable presence of lineage-specific transcription factors, as described in Caenorhabditis elegans⁸³ (Box 4). CLP, common lymphoid progenitor; DN, double negative (CD4⁻CD8⁻); DP, double positive (CD4⁺CD8⁺); ETP, early T cell progenitor; LMPP, lymphoid primed multipotent progenitor; T_reg cell, regulatory T cell.