Topic
MLL1 complex
About: MLL1 complex is a research topic. Over the lifetime, 20 publications have been published within this topic receiving 3126 citations.
Papers
TL;DR: It is shown that MLL regulates target Hox gene expression through direct binding to promoter sequences and the MLL SET domain is a histone H3 lysine 4-specific methyltransferase whose activity is stimulated with acetylated H3 peptides.
1,146 citations
TL;DR: This study reports the first biochemical reconstitution of a functional four-component mixed-lineage leukemia protein-1 (MLL1) core complex and demonstrates that WDR5 mediates interactions of the MLL1 catalytic unit both with the common structural platform and with the histone substrate.
Abstract: Histone H3 Lys4 (H3K4) methylation is a prevalent mark associated with transcription activation. A common feature of several H3K4 methyltransferase complexes is the presence of three structural components (RbBP5, Ash2L and WDR5) and a catalytic subunit containing a SET domain. Here we report the first biochemical reconstitution of a functional four-component mixed-lineage leukemia protein-1 (MLL1) core complex. This reconstitution, combined with in vivo assays, allows direct analysis of the contribution of each component to MLL1 enzymatic activity and their roles in transcriptional regulation. Moreover, taking clues from a crystal structure analysis, we demonstrate that WDR5 mediates interactions of the MLL1 catalytic unit both with the common structural platform and with the histone substrate. Mechanistic insights gained from this study can be generalized to the whole family of SET1-like histone methyltransferases in mammals.
798 citations
TL;DR: An activator-based mechanism for joint MLL1 and MOF recruitment and targetedmethylation and acetylation is indicated and a molecular explanation for the closely correlated distribution of H3 K4 methylation and H4 K16 acetylations on active genes is provided.
707 citations
TL;DR: In this article, a recently developed inhibitor MM-401 that targets the MLL1 H3K4 methyltransferase activity is presented, which is able to specifically inhibit MLL 1 activity by blocking MLL-WDR5 interaction and thus the complex assembly.
296 citations
TL;DR: The results suggest that the mechanism of multiple lysine methylation by the MLL1 core complex involves the sequential addition of two methyl groups at two distinct active sites within the complex.
266 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 3 |
| 2019 | 4 |
| 2018 | 1 |
| 2017 | 1 |
| 2016 | 4 |
| 2014 | 2 |