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Genome-wide assessment of REST binding profiles reveals distinctions between human and mouse hippocampus

McGann, J. C.; Spinner, M. A.; Garg, S. K.; Mullendorf, K.; Woltjer, R. L.; Mandel, G.

2020-07-07 genomics
10.1101/2020.07.07.192229 bioRxiv
Show abstract

Background The transcriptional repressor, RE1 Silencing Transcription Factor (REST), recognized historically as a master regulator of neuronal gene expression during mouse development, has recently been ascribed roles in human aging and neurodegenerative disorders. However, REST’s role in healthy adult human brain, and how faithfully mouse models reproduce REST function in human brain, is not known.Results Here, we present the first genome-wide binding profile for REST in both mouse and human postnatal hippocampus. We find the majority of REST-bound sites in human hippocampus are unique compared to both mouse hippocampus and to all other reported human ENCODE cell types. Genes associated with unique REST-bound sites include previously unidentified categories related to innate immunity and inflammation signaling, suggesting species specific roles for REST in protecting human brain health.Conclusions Our results suggest newly evolved functions for REST in maintaining human brain health.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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