DNMT1 in Six2 progenitor cells is essential for transposable element silencing and kidney development. 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