Crucial roles for interactions between MLL3/4 and INI1 in nuclear receptor transactivation

Seunghee Lee, Dae Hwan Kim, Young Hwa Goo, Young Chul Lee, Soo-Kyung Lee, Jae Lee

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Nuclear receptor (NR) transactivation involves multiple coactivators, and the molecular basis for how these are functionally integrated needs to be determined to fully understand the NR action. Activating signal cointegrator-2 (ASC-2), a transcriptional coactivator of many NRs and transcription factors, forms a steady-state complex, ASCOM (for ASC-2 complex), which contains histone H3-lysine-4 (H3K4) methyltransferase MLL3 or its paralog MLL4. Here, we show that ASCOM requires a functional cross talk with the ATPase-dependent chromatin remodeling complex Swi/ Snf for efficient NR transactivation. Our results reveal that ASCOM and Swi/Snf are tightly colo- calized in the nucleus and that ASCOM and Swi/Snf promote each other's binding to NR target genes. We further show that the C-terminal SET domain of MLL3 and MLL4 directly interacts with INI1, an integral subunit of Swi/Snf. Our mutational analysis demonstrates that this interaction underlies the mutual facilitation of ASCOM and Swi/Snf recruitment to NR target genes. Importantly, this study uncovers a specific protein-protein interaction as a novel venue to couple two distinct enzymatic coactivator complexes during NR transactivation.

Original languageEnglish (US)
Pages (from-to)610-619
Number of pages10
JournalMolecular Endocrinology
Volume23
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

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Cytoplasmic and Nuclear Receptors
Transcriptional Activation
Chromatin Assembly and Disassembly
Methyltransferases
Histones
Genes
Lysine
Adenosine Triphosphatases
Proteins
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Crucial roles for interactions between MLL3/4 and INI1 in nuclear receptor transactivation. / Lee, Seunghee; Kim, Dae Hwan; Goo, Young Hwa; Lee, Young Chul; Lee, Soo-Kyung; Lee, Jae.

In: Molecular Endocrinology, Vol. 23, No. 5, 05.2009, p. 610-619.

Research output: Contribution to journalArticle

Lee, Seunghee ; Kim, Dae Hwan ; Goo, Young Hwa ; Lee, Young Chul ; Lee, Soo-Kyung ; Lee, Jae. / Crucial roles for interactions between MLL3/4 and INI1 in nuclear receptor transactivation. In: Molecular Endocrinology. 2009 ; Vol. 23, No. 5. pp. 610-619.
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