Transcription factors Tp73, Cebpd, Pax6, and Spi1 rather than DNA methylation regulate chronic transcriptomics changes after experimental traumatic brain injury

Acta Neuropathologica Communications
Anssi LipponenAsla Pitkänen

Abstract

Traumatic brain injury (TBI) induces a wide variety of cellular and molecular changes that can continue for days to weeks to months, leading to functional impairments. Currently, there are no pharmacotherapies in clinical use that favorably modify the post-TBI outcome, due in part to limited understanding of the mechanisms of TBI-induced pathologies. Our system biology analysis tested the hypothesis that chronic transcriptomics changes induced by TBI are controlled by altered DNA-methylation in gene promoter areas or by transcription factors. We performed genome-wide methyl binding domain (MBD)-sequencing (seq) and RNA-seq in perilesional, thalamic, and hippocampal tissue sampled at 3 months after TBI induced by lateral fluid percussion in adult male Sprague-Dawley rats. We investigated the regulated molecular networks and mechanisms underlying the chronic regulation, particularly DNA methylation and transcription factors. Finally, we identified compounds that modulate the transcriptomics changes and could be repurposed to improve recovery. Unexpectedly, DNA methylation was not a major regulator of chronic post-TBI transcriptomics changes. On the other hand, the transcription factors Cebpd, Pax6, Spi1, and Tp73 were upregulated...Continue Reading

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Citations

Jun 18, 2020·Nature Reviews. Neurology·Gary P Brennan, David C Henshall
Dec 16, 2020·Neural Regeneration Research·Meng-Shi YangBai-Yun Liu
Dec 2, 2020·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Long-Yan RanZhi-Zhong Guan
Jul 18, 2021·Acta neurochirurgica·Sami Abu HamdehNiklas Marklund
Aug 31, 2021·Journal of Immunology Research·Xiaoyun LiYuan Yang

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Datasets Mentioned

BETA
GSE80174
GSE107837
BIIB021

Methods Mentioned

BETA
pharmacotherapy
MBD-seq
RNA-seq
electrophoresis
PCR
pharmacotherapies

Software Mentioned

blocksStats
R package
LINCS
R
Signalink
GSEA
DEseq2
Illumina Off - Line Basecaller
Gene Set Enrichment Analysis ( GSEA )
FastQC

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