Navegando por Palavras-chave "Epigenetic Repression"

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    Identificação De Ge-Nes Regulados Por Ac-Etilação De H3K9 Em Cérebros De Pacientes Com Doença De Alzh-Eimer: Uma Abordagem Por Chip-Seq
    (Universidade Federal de São Paulo (UNIFESP), 2017-08-31) Santana, Dalileia Aparecida [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    To identify genes regulated by H3K9 acetylation in brain samples of individuals affected by Alzheimer’s disease, in comparison to elderly controls, by ChIP-Seq. Methods: Our sample consisted of brain tissue from three brain regions (auditory cortex, hippocampus and cerebellum) from 6 Alzheimer’s disease patients and 6 elderly controls. The samples underwent enzymatic digestion for ChIP-Seq assay. The samples were pooled into 6 groups, according to the region and the group, for the library preparation step. The libraries were sequenced using HiSeq 2500, in Rapid Run mode, single-end reads (1 x 66 pb). Two bioinformatics analyses were carried out: in the first, standard parameters were used in the pipeline; in the second, adjustments were made in the pipeline. Three genes identified in the first analysis were selected for real-time PCR confirmation: CHM, GRIP1 and MIR4735. In silico analysis of the gene network was performed by GIANT database. Results: The analysis with standard parameters yielded a list of 14 genes with decreased level of H3K9 acetylation in Alzheimer group compared to controls. The analysis with adjustments in the pipeline showed that 17 genes present decreased level and 71 genes present increased level of acetylation of H3K9 in the Alzheimer group in comparison to the control group. qPCR confirmation of CHM, GRIP1 and MIR4735 genes did not show difference in the level of H3K9 acetylation between groups. Motifs discovery demonstrated associated transcription factors for both groups. In silico analysis demonstrated an interaction of CHM and GRIP1 genes with each other and with APOE and PSEN2 genes. In addition, an interaction between ACHE and PSEN2, between ADRA2A, PSEN2 and APP, between ATP12A, APOE, PSEN2 and APP, and between ARSB, PSEN2 and APP was found. Conclusion: To our knowledge, this is the first study to evaluate H3K9 acetylation in Alzheimer’s disease using ChIP-Seq. The analysis with the pipeline adjustments represented our samples more efficiently. Thus, our findings have shown that 17 genes were less acetylated and 71 genes were more acetylated in H3K9 in brain samples of individuals from the Alzheimer group when compared to individuals from the control group. Taken together, these results show the importance of studying such alterations to a better understanding of the Alzheimer’s disease pathology.