Thus, we demonstrate that native CMS progenitor cells produce a larger proportion of erythroid precursors under hypoxia and that SENP1 is essential for proliferation.
Closer examination of individual genes in these regions revealed the involvement of previously identified candidates (e.g., SENP1) and also unreported ones SGK3, COPS5, PRDM1, and IFT122 in CMS.
The SENP1 gene encodes for a protease that regulates the function of hypoxia-relevant transcription factors such as Hypoxia-Inducible Factor (HIF) and GATA, and thus might have an erythropoietic regulatory role in CMS through the modulation of the expression of erythropoietin (Epo) or Epo receptors.
SENP1 reverses the hormone-augmented SUMOylation of androgen receptor (AR) increasing the transcription activity of AR.In conclusion, increased androgen activity is related with CMS.
Our results provide independent evidence in support of a role for SENP1 in CMS in individuals of Quechua ancestry and suggest the SENP1 and ANP32D signatures of selection are in tight linkage disequilibrium (LD).