Our data show that histone methyltransferase SETDB1 is critical for preventing transcription factor (TF) activity on nonphysiological binding sites, in part overlapping with mouse endogenous retrovirus sequences. When SETDB1 is lacking, these cryptic enhancers can become overly active, leading to abnormal expression of nearby genes. This disruption coincides with compromised function of stem cells, altered differentiation of blood cell types, and increased hematopoietic stem cell proliferation. Notably, we demonstrate that SETDB1 acts as a guardian, restricting the unwarranted activity of TFs on these cryptic enhancers and maintaining the proper balance and differentiation of mouse fetal liver hematopoietic stem and progenitor cells.
published in PNAS
The Schotta Lab 