title: Binding of transcription factors to Presenilin 1 and 2 promoter cis-acting elements varies during the development of mouse cerebral cortex.
abstract: Previously, we reported differential expression of Presenilin (PS)1 and 2 and epigenetic modifications of their gene promoter in the cerebral cortex of mice during development. We identified the crucial role of DNA methylation and H3K9/14 acetylation in stage specific PS expression during brain development. Interestingly, we noted differential DNA methylation in putative binding sites of transcription factors considered pivotal for brain development. This prompted us to study the binding of transcription factors to cis-acting elements of PS1 and PS2 promoter in the cerebral cortex of mice during development. In-silico analysis revealed various cis-acting elements of PS1 and PS2 promoter and their putative transcription factors. We selected those cis-acting elements that were proven by wet lab experiments to interact with the transcription factors crucial for brain development. Electrophoretic mobility shift assay revealed that the binding of nuclear proteins to PS1 promoter cis-acting elements like HSF-1, Cdx1, Ets-1 and Sp1 significantly increased at embryonic day (E) 12.5, postnatal day (P) 45 and 20 weeks (w) as compared to P0. The binding pattern of these factors correlated well with the PS1 expression profile, indicating their cumulative influence on PS1 gene transcription. For PS2 promoter, the binding of Nkx2.2 and HFH-2 was high at prenatal stages (E12.5 and E18.5) while that of Cdx1 and NF-κB was maximum at postnatal stages (P45 and 20w). Taken together, our study shows that the binding of HSF-1, Cdx1, Ets-1 and Sp1 to PS1 promoter and that of Nkx2.2, HFH-2, Cdx1 and NF-κB to PS2 promoter regulate their differential expression during brain development.
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, Postcode-221 005, India; Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, Postcode-474 011, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, Postcode-221 005, India. Electronic address: mkt_bhu@yahoo.com.
authors.forename: M K
authors.initials: MK
authors.lastname: Thakur
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: C491272:Cdx1 protein, mouse; D004268:DNA-Binding Proteins; C494042:Ets1 protein, mouse; D051858:Forkhead Transcription Factors; C101757:Foxd3 protein, mouse; D000076249:Heat Shock Transcription Factors; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C490017:Hsf1 protein, mouse; D016328:NF-kappa B; C000715627:Nkx2-2 protein, mouse; D053764:Presenilin-1; D053766:Presenilin-2; D050784:Proto-Oncogene Protein c-ets-1; C095101:Psen2 protein, mouse; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish; C580804:presenilin 1, mouse
keywords: Brain development; Electrophoretic mobility shift assay; PS expression; PS promoter