PRDM16 (PR domain containing 16)

1p36.32

11 splice variants

1276 amino acids and smaller proteins. Contains a N-term PR domain; 7 Zinc fingers, a proline-rich domain, and 3 Zinc fingers in the C-term. Binds DNA. Transcription activator; PRDM16 has an intrinsic histone methyltransferase activity. PRDM16 forms a transcriptional complex with CEBPB. PRDM16 plays a downstream regulatory role in mediating TGFB signaling (Bjork et al., 2010). PRDM16 induces brown fat determination and differentiation. PRDM16 is expressed selectively in the earliest stem and progenitor hematopoietic cells, and is required for the maintenance of the hematopoietic stem cell pool during development. PRDM16 is also required for survival, cell-cycle regulation and self-renewal in neural stem cells (Chuikov et al., 2010; Kajimura et al., 2010; Aguilo et al., 2011; Chi and Cohen, 2016).

SKI (SKI proto-oncogene)

1p36.33

Negative regulator of the TGFB)/Smad signaling. SKI and SKIL (SnoN) are transcriptional co-repressors which interact with Smads, and repress transcription induced by TGFB. TGFB signaling suppresses tumor cell proliferation at early stages of tumorigenesis but promotes epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastasis at late malignant stages. SKI interacts with the Hippo pathway. SKI inhibites the transcription activity of TAZ as well as its ability to promote transformation and EMT (Rashidian et al., 2015). High expression of SKI results in activation of hematopoietic stem cells transcriptional programs and an HSC autonomous repopulating advantage that favors myeloid development through hepatocyte growth factor (HGF) signaling and independently of its ability to inhibit TGFB signaling. SKI is highly expressed in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) (Singbrant et al., 2014). SKI has a critical role in the development of neuronal and muscle cells or tissues. SKI mutations have been identified in Shprintzen-Goldberg syndrome (SGS) (Schepers et al., 2015).