title: CBX8, a component of the Polycomb PRC1 complex, modulates DOT1L-mediated gene expression through AF9/MLLT3.
abstract: AF9 is known to interact with multiple proteins including activators and repressors of transcription. Our data indicate that other AF9 binding proteins compete with the histone methyltransferase DOT1L for AF9 binding thus diminishing its ability to methylate lysine 79 of histone 3. Specifically, we show that AF9 is part of a protein multimer containing members of Polycomb group (PcG) PRC1 complex, CBX8, RING1B, and BMI1. Interaction with CBX8 precludes AF9-DOT1L binding. Knockdown of CBX8 with short-hairpin RNA (shRNA) leads to decreased expression of the AF9 target gene ENaCα. In contrast, CBX8 overexpression results in increased ENaCα mRNA levels and this effect can be partially overcome by co-overexpression of AF9.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Malik
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hemenway
mesh_terms: D045744:Cell Line, Tumor; D053503:Epithelial Sodium Channels / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000737:chemistry; D011485:Protein Binding; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C570428:CBX8 protein, human; D053503:Epithelial Sodium Channels; C489901:MLLT3 protein, human; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C473477:DOT1L protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D063150:Polycomb Repressive Complex 1
keywords: CTD; ChIP; ENaCα; Gene regulation; H3K79; Histone methylation; PRC1; PcG; PcG repressive complex 1; Polycomb-group protein; carboxy-terminal domain; chromatin immunoprecipitation; histone 3 lysine 79; polycomb group; qRT-PCR; quantitative reverse transcriptase polymerase chain reaction; shRNA; short-hairpin RNA
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