SETD7 regulates the differentiation of human embryonic stem cells

The successful use of specialized cells in regenerative medicine requires an optimization in the differentiation protocols that are currently used. Understanding the molecular events that take place during the differentiation of human pluripotent cells is essential for the improvement of these protocols and the generation of high quality differentiated cells. In an effort to understand the molecular mechanisms that govern differentiation we identify the methyltransferase SETD7 as highly induced during the differentiation of human embryonic stem cells and differentially expressed between induced pluripotent cells and somatic cells. Knock-down of SETD7 causes differentiation defects in human embryonic stem cell including delay in both the silencing of pluripotency-related genes and the induction of differentiation genes. We show that SETD7 methylates linker histone H1 in vitro causing conformational changes in H1. These effects correlate with a decrease in the recruitment of H1 to the pluripotency genes OCT4 and NANOG during differentiation in the SETD7 knockdown that might affect the proper silencing of these genes during differentiation.M.J.B. was partially supported by the Ramón y Cajal program of MEC (RYC-2007-01510). B.S. was a recipient of a predoctoral fellowship from MEC (BES-2008-009567). C.M. was supported by PT13/0001/0041 PRB2-ISCIII-SGEFI- FEDER-PE I+D+i 2013-2016. J.C. was partially supported by Fundación CELLEX. This work was partially supported by grant RD12/0019/0034 TERCEL-RETICS-ISCIII-MINECO-FEDER, grant SAF2009-08588 from MICINN to M.J.B and grant BFU2014-52237 to A.J.Peer Reviewe