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

Nat Struct Mol Biol. 2011 Nov 13;18(12):1358-65. doi: 10.1038/nsmb.2153.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Chromatin Assembly and Disassembly
  • DNA Helicases / metabolism
  • DNA Helicases / physiology
  • Enhancer Elements, Genetic*
  • Estrogen Receptor alpha / metabolism
  • Estrogens / metabolism
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / physiology*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism*
  • Humans
  • Lysine / chemistry
  • Lysine / metabolism
  • Lysine Acetyltransferase 5
  • Methylation
  • Molecular Sequence Data
  • Myeloid-Lymphoid Leukemia Protein / metabolism
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Protein Interaction Mapping
  • Sequence Alignment
  • Transcription Factors / metabolism
  • Transcription Factors / physiology
  • Transcriptional Activation*


  • Estrogen Receptor alpha
  • Estrogens
  • Histones
  • KMT2A protein, human
  • Nuclear Proteins
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • Setd1A protein, human
  • Histone Acetyltransferases
  • KAT5 protein, human
  • Lysine Acetyltransferase 5
  • SMARCA4 protein, human
  • DNA Helicases
  • Lysine