title: Topoisomerase I inhibition leads to length-dependent gene expression changes in human primary astrocytes.
abstract: Topoisomerase I is required for the proper expression of long genes (> 100 kb) in mouse and human cortical neurons, including many candidate genes for autism spectrum disorder (ASD) [1]. Given the important role of astrocytes in brain development [2], we investigated whether long genes, including autism susceptibility genes, also require topoisomerase I expression in human primary astrocytes. We carried genome-wide expression profiling of cultured human primary astrocytes following treatment with the topoisomerase I inhibitor Topotecan, using Illumina microarrays. We identified several thousands of differentially expressed genes and confirmed that topoisomerase I inhibition affects gene expression in human primary astrocytes in a length-dependent manner. We also identified over 20 ASD-associated genes that show topoisomerase-dependent gene expression in human primary astrocytes but have not been previously reported as topoisomerase-I-dependent in neurons. The microarray data have been deposited in NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE90052.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Akira
authors.initials: A
authors.lastname: Gokoolparsadh
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Irina
authors.initials: I
authors.lastname: Voineagu