title: Human ALKBH4 interacts with proteins associated with transcription.
abstract: The Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from E. coli is a demethylase which repairs alkyl lesions in DNA, as well as RNA, through a direct reversal mechanism. Humans possess nine AlkB homologs (ALKBH1-8 and FTO). ALKBH2 and ALKBH3 display demethylase activities corresponding to that of AlkB, and both ALKBH8 and FTO are RNA modification enzymes. The biochemical functions of the rest of the homologs are still unknown. To increase our knowledge on the functions of ALKBH4 and ALKBH7 we have here performed yeast two-hybrid screens to identify interaction partners of the two proteins. While no high-confidence hits were detected in the case of ALKBH7, several proteins associated with chromatin and/or involved in transcription were found to interact with ALKBH4. For all interaction partners, the regions mediating binding to ALKBH4 comprised domains previously reported to be involved in interaction with DNA or chromatin. Furthermore, some of these partners showed nuclear co-localization with ALKBH4. However, the global gene expression pattern was only marginally altered upon ALKBH4 over-expression, and larger effects were observed in the case of ALKBH7. Although the molecular function of both proteins remains to be revealed, our findings suggest a role for ALKBH4 in regulation of gene expression or chromatin state.
authors.affiliation: Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Linn G
authors.initials: LG
authors.lastname: Bjørnstad
authors.forename: Trine J
authors.initials: TJ
authors.lastname: Meza
authors.forename: Marit
authors.initials: M
authors.lastname: Otterlei
authors.forename: Solveig M
authors.initials: SM
authors.lastname: Olafsrud
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
authors.forename: Pål Ø
authors.initials: PØ
authors.lastname: Falnes
mesh_terms: D000071501:AlkB Homolog 4, Lysine Demethylase; D002262:Carboxy-Lyases / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D004247:DNA / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D049308:Dioxygenases; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; C090862:ELL protein, human; D035602:Transcriptional Elongation Factors; D004247:DNA; D049308:Dioxygenases; C557720:ALKBH4 protein, human; D000071501:AlkB Homolog 4, Lysine Demethylase; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D002262:Carboxy-Lyases