MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [CUT&RUN]

MLL3 and MLL4 are the mjor histone lysine methyltransferases for the active enhance mark H3K4me1. We observed that platelet counts are dramatically decreased in the MLL3/4 SET-deletion mice. Cultured megakaryocytes from MLL3/4 SET-deletion fetal liver were used for RNA-seq analysis to investigate the changes in gene expression. We also performed CUT&RUN analysis to examine the changes in enhncers that may regulate those gene expression. We included PTIP in this study, because it is an important co-factor of the MLL3/4 complex, and knockout of PTIP also leads to decreased platelet production. 3 samples for each genotype were used for CUT&RUN using IgG control, anti-H3K4me1, anti-H3K27ac and anti-H3K4me3 antibodies.