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Recognition of enhancer element-specific histone methylation by TIP60 in transcriptional activation.

Many co-regulator proteins are recruited by DNA-bound transcription factors to remodel chromatin and activate transcription. However, mechanisms for coordinating actions of multiple co-regulator proteins are poorly understood. We demonstrate that multiple protein-protein interactions by the protein acetyltransferase TIP60 are required for estrogen-induced transcription of a subset of estrogen receptor alpha (ERα) target genes in human cells. Estrogen-induced recruitment of TIP60 requires direct binding of TIP60 to ERα and the action of chromatin-remodeling ATPase BRG1, leading to increased recruitment of histone methyltransferase MLL1 and increased monomethylation of histone H3 at Lys4. TIP60 recruitment also requires preferential binding of the TIP60 chromodomain to histone H3 containing monomethylated Lys4, which marks active and poised enhancer elements. After recruitment, TIP60 increases acetylation of histone H2A at Lys5. Thus, complex cooperation of TIP60 with ERα and other chromatin-remodeling enzymes is required for estrogen-induced transcription.

Pubmed ID: 22081016 RIS Download

Mesh terms: Amino Acid Sequence | Cell Line | Chromatin Assembly and Disassembly | DNA Helicases | Enhancer Elements, Genetic | Estrogen Receptor alpha | Estrogens | Histone Acetyltransferases | Histone-Lysine N-Methyltransferase | Histones | Humans | Lysine | Methylation | Molecular Sequence Data | Myeloid-Lymphoid Leukemia Protein | Nuclear Proteins | Protein Interaction Mapping | Sequence Alignment | Transcription Factors | Transcriptional Activation

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Associated grants

  • Agency: NHLBI NIH HHS, Id: R01 HL089726-04
  • Agency: NIGMS NIH HHS, Id: GM84209
  • Agency: NHLBI NIH HHS, Id: R01 HL089726
  • Agency: NIDDK NIH HHS, Id: R01 DK043093
  • Agency: NHLBI NIH HHS, Id: HL089726
  • Agency: NIGMS NIH HHS, Id: R01 GM084209
  • Agency: NIDDK NIH HHS, Id: DK43093
  • Agency: NHLBI NIH HHS, Id: R01 HL089726-02S1

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