Shashank Kumar Maurya1, Rajnikant Mishra1. 1. Department of Zoology, Biochemistry and Molecular Biology Laboratory, Institute of Science, Banaras Hindu University, Varanasi, India.
Abstract
BACKGROUND: Patients having mutations of Pax6 bear phenotypes that match age-associated neurological disorders. Mutations affect most cellular functions such as cell division, growth, differentiation, and cell death in brain, eyes, pituitary, pineal, and pancreas. The progressive reduction in the level of Pax6 during aging has also been observed. However, information about downstream targets of Pax6 in brain is unclear. Therefore, it is presumed that age-dependent alterations of Pax6 may also affect cascades of promoter sequence recognition in brain during aging. PURPOSE: This study is aimed at studying the interaction of Pax6 with DNA sequence elements to explore alteration in gene targets and transcription networks of Pax6 in brain during aging. METHODS: Chromatin immunoprecipitation with anti-Pax6 using tissue extracts of brain from newborn, young, adult, and old mice was done. Pulled DNA from brain was analysed by gene-specific polymerase chain reaction (PCR). Amplified PCR products were sequenced and analyzed. RESULTS: Age-associated alterations in binding to genetic sequence elements by Pax6 were observed. Promoter analysis predicts genes involved in neuronal survival (Bdnf, Sparc), specificity of astrocyte (S100β, Gfap), cell-proliferation (Pcna), inflammation and immune response (interferon-γ, tumour necrosis factor-α), management of oxidative stress (Sod, Cat), and hypoxia (Ldh). CONCLUSION: The Pax6 either directly or indirectly binds to promoter sequences of genes essential for immunological surveillance and energy metabolism in brain that alters during aging.
BACKGROUND:Patients having mutations of Pax6 bear phenotypes that match age-associated neurological disorders. Mutations affect most cellular functions such as cell division, growth, differentiation, and cell death in brain, eyes, pituitary, pineal, and pancreas. The progressive reduction in the level of Pax6 during aging has also been observed. However, information about downstream targets of Pax6 in brain is unclear. Therefore, it is presumed that age-dependent alterations of Pax6 may also affect cascades of promoter sequence recognition in brain during aging. PURPOSE: This study is aimed at studying the interaction of Pax6 with DNA sequence elements to explore alteration in gene targets and transcription networks of Pax6 in brain during aging. METHODS: Chromatin immunoprecipitation with anti-Pax6 using tissue extracts of brain from newborn, young, adult, and old mice was done. Pulled DNA from brain was analysed by gene-specific polymerase chain reaction (PCR). Amplified PCR products were sequenced and analyzed. RESULTS: Age-associated alterations in binding to genetic sequence elements by Pax6 were observed. Promoter analysis predicts genes involved in neuronal survival (Bdnf, Sparc), specificity of astrocyte (S100β, Gfap), cell-proliferation (Pcna), inflammation and immune response (interferon-γ, tumour necrosis factor-α), management of oxidative stress (Sod, Cat), and hypoxia (Ldh). CONCLUSION: The Pax6 either directly or indirectly binds to promoter sequences of genes essential for immunological surveillance and energy metabolism in brain that alters during aging.
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