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DOT1L complex regulates transcriptional initiation in human cells

ABSTRACT: DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17 and ENL/AF9, is dysregulated in most of the cases of mixed lineage leukemia (MLL) and is believed to regulate transcriptional elongation without much evidence. Here we show that the depletion of DOT1L reduced the global occupancy without affecting the traveling ratio or the elongation rate of Pol II, suggesting it not a major player in elongation. An examination of general transcription factors (GTFs) binding revealed globally reduced TBP and TFIIA occupancies near promoters after DOT1L loss, pointing to a role in transcriptional initiation. Proteomic studies uncovered that DOT1L regulates transcriptional initiation likely by facilitating the recruitment of TFIID. Moreover, we found that ENL also regulates transcriptional initiation and that DOT1L stimulates H2B monoubiquitination by limiting the recruitment of human SAGA complex. These results advanced current understanding of epigenetic regulation of transcriptional initiation and roles of DOT1L complex in MLL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161367 | GEO | 2021/06/17

REPOSITORIES: GEO

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Expression changes after Inhibition of AHD in Molm-13 cells

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Transcription control by the ENL YEATS domain in acute leukemia [ChIP-seq]

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Degree of Recruitment of DOT1L to MLL-AF9 Defines Level of H3K79 Di- and Tri-methylation on Target Genes and Transformation Potential

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Transcription Initiation Platforms and GTF recruitment at tissue-specific enhancers and promoters

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