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Full-Text Articles in Medical Sciences
The Histone Methyltransferase Activity Of Mll1 Is Dispensable For Hematopoiesis And Leukemogenesis, Bibhu Mishra, Kristin M. Zaffuto, Erika L. Artinger, Tonis Org, Hannah K. A. Mikkola, Chao Cheng, Malek Djabali
The Histone Methyltransferase Activity Of Mll1 Is Dispensable For Hematopoiesis And Leukemogenesis, Bibhu Mishra, Kristin M. Zaffuto, Erika L. Artinger, Tonis Org, Hannah K. A. Mikkola, Chao Cheng, Malek Djabali
Dartmouth Scholarship
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 supporting leukemogenesis driven by the MLL-AF9 fusion oncoprotein. Upon Mll1 deletion, histone H4 lysine 16 (H4K16) acetylation is selectively depleted at MLL1 target genes in conjunction with reduced transcription. Surprisingly, inhibition of SIRT1 is sufficient …