title: Stimulation of ribosomal RNA gene promoter by transcription factor Sp1 involves active DNA demethylation by Gadd45-NER pathway.
abstract: The well-studied Pol II transcription factor Sp1 has not been investigated for its regulatory role in rDNA transcription. Here, we show that Sp1 bound to specific sites on rDNA and localized into the nucleoli during the G1 phase of cell cycle to activate rDNA transcription. It facilitated the recruitment of Pol I pre-initiation complex and impeded the binding of nucleolar remodeling complex (NoRC) to rDNA resulting in the formation of euchromatin active state. More importantly, Sp1 also orchestrated the site-specific binding of Gadd45a-nucleotide excision repair (NER) complex resulting in active demethylation and transcriptional activation of rDNA. Interestingly, knockdown of Sp1 impaired rDNA transcription due to reduced engagement of the Gadd45a-NER complex and hypermethylation of rDNA. Thus, the present study unveils a novel role of Sp1 in rDNA transcription involving promoter demethylation.
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Rajput
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Pandey
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India. Electronic address: vijay@icgeb.res.in.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000072283:A549 Cells; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002466:Cell Nucleolus / Q000378:metabolism; D019175:DNA Methylation; D004260:DNA Repair; D004275:DNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D022041:Euchromatin / Q000737:chemistry / Q000378:metabolism; D016193:G1 Phase; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012335:RNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D004275:DNA, Ribosomal; D022041:Euchromatin; D049452:Green Fluorescent Proteins; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C108209:SP1 protein, human; C485184:enhanced green fluorescent protein
keywords: DNA demethylation; Epigenetic regulation; Gadd45; Nucleolar remodeling complex; Ribosomal RNA; Ribosome biogenesis; Sp1