title: The zinc finger proteins ZNF644 and WIZ regulate the G9a/GLP complex for gene repression.
abstract: The G9a/GLP complex mediates mono- and dimethylation of Lys9 of histone H3 at specific gene loci, which is associated with transcriptional repression. However, the molecular mechanism by which the G9a/GLP complex is targeted to the specific gene loci for H3K9 methylation is unclear. In this study, with unbiased protein affinity purification, we found ZNF644 and WIZ as two core subunits in the G9a/GLP complex. ZNF644 and WIZ interact with the transcription activation domain of G9a and GLP, respectively. Moreover, both ZNF644 and WIZ contain multiple zinc finger motifs that recognize consensus DNA sequences. ZNF644 and WIZ target G9a and GLP to the chromatin and mediate the G9a/GLP complex-dependent H3K9 methylation as well as gene repression. Thus, our studies reveal two key subunits in the G9a/GLP complex that regulate the function of this histone methyltransferase complex.
authors: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Chunjing
authors: C
authors: Bian
authors: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Qiang
authors: Q
authors: Chen
authors: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
authors: Xiaochun
authors: X
authors: Yu
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006649:Histocompatibility Antigens / Q000235:genetics* / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D002843:Chromatin; D006649:Histocompatibility Antigens; D006657:Histones; D051741:Kruppel-Like Transcription Factors; D046912:Multiprotein Complexes; D014157:Transcription Factors; C000604247:WIZ protein, human; C573234:ZNF644 protein, human; C455847:EHMT1 protein, human; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine
keywords: G9a; H3K9 methylation; biochemistry; epigenetic modification; human; zinc finger motif