Project description:This study describes the transcriptome profiling of: 1) Mll1fl/fl mESCs in LIF/Serum medium as control; 2) Mll1fl/fl mESCs with 4-OHT (Mll1-/-), MM-401 (Mll1i) in LIF/serum medium ; 2) Mll1fl/fl mESCs with 2i in LIF/serum-free (KSR) medium.
Project description:This study describes the single-cell transcriptome profiling of: 1) Mll1fl/fl mESCs as control; 2) Mll1fl/fl mESCs with 4-OHT (Mll1-/-) or with MM-401 (Mll1i) in LIF/15KSR/5% serum KO DMEM medium on Matrigel.
Project description:We report Illumina next generation RNA sequencing (RNAseq) of NUP98-HOXA9 in vitro transformed murine LSKs upon genetic deletion of Mll1. These gene expression data illustrate that Mll1 regulates Hoxa, Hoxb and Meis1 expression in NUP98-HOXA9 transformed murine BM cells.
Project description:Despite correlations between histone methyltransferase (HMT) activity and gene regulation, direct evidence that HMT activity is responsible for gene activation is sparse. We address the role of the HMT activity for MLL1, a histone H3 lysine 4 (H3K4) methyltransferase critical for maintaining hematopoietic stem cells (HSCs). Here we show that the SET domain and thus HMT activity of MLL1 is dispensable for maintaining HSCs and for supporting leukemogenesis driven by the MLL-AF9 fusion oncoprotein. Upon Mll1 deletion, histone H4 lysine 16 (H4K16) acetylation was selectively depleted at MLL1 target genes in conjunction with reduced transcription. Surprisingly, inhibition of SIRT1 was sufficient to prevent the loss of H4K16 acetylation and the reduction in MLL1 target gene expression. Thus, recruited MOF activity, and not the intrinsic HMT activity of MLL1, is central for the maintenance of HSC target genes. In addition, this work reveals a role for SIRT1 in opposing MLL1 function. 11 Samples, 5 controls and 5 KOs with antibodies H3K4me1, H3K4me3, and H3K27Ac. One input Sample.