Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferase

Seunghee Lee, Dong Kee Lee, Yali Dou, Jeongkyung Lee, Bora Lee, Eunyee Kwak, Young Yun Kong, Soo Kyung Lee, Robert G. Roeder, Jae W. Lee

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Activating signal cointegrator-2 (ASC-2), a coactivator of multiple transcription factors that include retinoic acid receptor (RAR), associates with histone H3-K4 methyltranferases (H3K4MTs) MLL3 and MLL4 in mixed-lineage leukemia. Here, we show that mice expressing a SET domain mutant of MLL3 share phenotypes with isogenic ASC2+/- mice and that expression and H3-K4 trimethylation of RAR target gene RAR-β2 are impaired in ASC-2-null mouse embryo fibroblasts (MEFs) or in MEFs expressing siRNAs against both MLL3 and MLL4. We also show that MLL3 and MLL4 are found in distinct ASC-2-containing complexes rather than in a common ASC-2 complex, and they are recruited to RAR-β2 by ASC-2. In contrast, RAR-β2 expression is intact in MEFs devoid of menin, a component of MLL1 and MLL2 H3K4MT complexes. These results suggest that ASC-2 confers target gene specificity to MLL3 and MLL4 H3K4MT complexes and that recruitment of H3K4MTs to their target genes generally involves interactions between integral components of H3K4MT complexes and transcription factors.

Original languageEnglish (US)
Pages (from-to)15392-15397
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number42
DOIs
StatePublished - Oct 17 2006

Keywords

  • Mixed-lineage leukemia (MLL)
  • Retinoic acid receptor
  • Transcription

ASJC Scopus subject areas

  • General

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