title: Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3.
abstract: Active DNA demethylation regulates epigenetic gene activation in numerous processes, but how the target site specificity of DNA demethylation is determined and what factors are involved are still poorly understood. Here we show that the tumor suppressor inhibitor of growth protein 1 (Ing1) is required for targeting active DNA demethylation. Ing1 functions by recruiting the regulator of DNA demethylation growth arrest and DNA damage protein 45a (Gadd45a) to histone H3 trimethylated at Lys 4 (H3K4me3). We show that reduced H3K4 methylation impairs recruitment of Gadd45a/Ing1 and gene-specific DNA demethylation. Our results indicate that histone methylation directs DNA demethylation.
authors: Institute of Molecular Biology, 55128 Mainz, Germany. a.schaefer@imb-mainz.de
authors: Andrea
authors: A
authors: Schäfer
authors: Emil
authors: E
authors: Karaulanov
authors: Ulrike
authors: U
authors: Stapf
authors: Gabi
authors: G
authors: Döderlein
authors: Christof
authors: C
authors: Niehrs
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019175:DNA Methylation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097642:GADD45 Proteins
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; D006657:Histones; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C501503:ING1 protein, human; C072012:MAGEB2 protein, human
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