Roles of histone H3-lysine 4 methyltransferase complexes in NR-mediated gene transcription.
Transcriptional regulation by nuclear hormone receptors (NRs) requires multiple coregulators that modulate chromatin structures by catalyzing a diverse array of posttranslational modifications of histones. Different combinations of these modifications yield dynamic functional outcomes, constituting an epigenetic histone code. This code is inscribed by histone-modifying enzymes and decoded by effector proteins that recognize specific covalent marks. One important modification associated with active chromatin structures is methylation of histone H3-lysine 4 (H3K4). Crucial roles for this modification in NR transactivation have been recently highlighted through our purification and subsequent characterization of a steady-state complex associated with ASC-2, a coactivator of NRs and other transcription factors. This complex, designated ASCOM for ASC-2 complex, contains H3K4-methyltransferase MLL3/HALR or its paralogue MLL4/ALR and represents the first Set1-like H3K4-methyltransferase complex to be reported in vertebrates. This review focuses on recent progress in our understanding of how ASCOM-MLL3 and ASCOM-MLL4 influence NR-mediated gene transcription and of their physiological function.
Lee
Seunghee
S
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Roeder
Robert G
RG
Lee
Jae W
JW
D000818:Animals; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014158:Transcription, Genetic
D006657:Histones; D046912:Multiprotein Complexes; D018160:Receptors, Cytoplasmic and Nuclear; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine