GSE110481
DNMT1 in Six2 progenitor cells is essential for transposable element silencing and kidney development
Cytosine methylation (5mC) plays a key role in maintaining progenitor cell self-renewal and differentiation. Here, we analyzed the role of 5mC in kidney development by genome-wide methylation and expression profiling and by systematic genetic targeting of DNA methyltransferases (Dnmt) and Tet eleven hydroxylases (Tet). In mice, nephrons differentiate from Six2+ progenitor cells, therefore we created animals with genetic deletion of Dnmt 1, 3a, 3b, Tet1, or Tet2 in the Six2+ population (Six2Cre/Dnmt1flox/flox, Six2Cre/Dnmt3aflox/flox, Six2Cre/Dnmt3bflox/flox, Six2Cre/Tet2flox/flox or Tet1-/-). Genome-wide methylation analysis indicated marked loss of methylation of transposable elements in Dnmt1 knock-out mice. RNA sequencing detected dedifferention of progenitor cells andtranscription of  endogenous retroviral genes transcripts. Overall design: RRBS for P0 Dnmt1 f/f, P0 Six2Cre Dnmt1 f/f and adult wild type mice. mRNA sequencing for P0 Dnmt1 f/f and Six2Cre Dnmt1 f/f