Journal
BLOOD
Volume 110, Issue 13, Pages 4445-4454Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-05-090514
Keywords
-
Categories
Funding
- NCI NIH HHS [CA92251, CA78815, R01 CA078815, R01 CA092251] Funding Source: Medline
Ask authors/readers for more resources
Chimeric proteins joining the histone methyltransferase MLL with various fusion partners trigger distinctive lymphoid and myeloid leukemias. Here, we immunopurified proteins associated with ENL, a protein commonly fused to MILL. Identification of these ENIL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase 11 C-terminal domain kinase [RNAPoIII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltrans-ferase DOTIL) as well as other frequent MILL partners (AF4, AlF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR). The composition of EAP was further verified by coimmunoprecipitation, 2-hybrid analysis, pull-down, and colocalization experiments. Purified EAP showed a histone H3 lysine 79-specific methylase activity, displayed a robust RNAPoIII CTD kinase function, and counteracted the effect of the pTEFb inhibitor 5,6-dichloro-benzimidazole-riboside. In vivo, an ENL knock-down diminished genome-wide as well as gene-specific H3K79 dimethylation, reduced global run-on elongation, and inhibited transient transcriptional reporter activity. According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available