Figure 5. Model: HDAC1 is crucial during early differentiation.

. Loss of HDAC1 in pluripotent cells inhibits their ability to differentiate by suppressing the histone deacetylation of promoters of pluripotency associated genes, therefore resulting in their sustained expression and as a consequence repressed lineage specific differentiation. The prolonged expression of these pluripotency-associated genes results in continuous repression of Sox-17 which in turn in needed to induce expression of BMP2 in differentiating cells. As BMP2 is not expressed, expression of key cardiovascular transcription factors is not achieved, resulting in reduced or absent cardiovascular differentiation.