Molecular basis for chromatin binding and regulation of MLL5

ABSTRACT: The human mixed lineage leukemia 5 (MLL5) protein mediates hematopoietic cell homeostasis, cell cycle and survival, however, the molecular basis underlying MLL5 activities remains unknown. Here, we show that MLL5 is recruited to gene-rich euchromatic regions via the interaction of its PHD finger with the histone mark H3K4me3. The 1.48 Å resolution crystal structure of the MLL5 PHD finger in complex with the H3K4me3 peptide reveals a non-canonical binding mechanism, whereby K4me3 is recognized through a single aromatic residue and an aspartate. The binding induces a His-Asp swapping rearrangement mediated by a C-terminal α-helix. Phosphorylation of H3T3 and H3T6 abrogates the association with H3K4me3 in vitro and in vivo, releasing MLL5 from chromatin in mitosis. This regulatory switch is

ORGANISM(S): Mus musculus

SUBMITTER: Hector Rincon-Arano 

PROVIDER: E-GEOD-47100 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress