FANCD2 genome binding is nonrandom and is enriched at large transcriptionally active neural genes prone to copy number variation.

Autor: Blaize JL; Department of Cell and Molecular Biology, University of Rhode Island, 379 Center for Biotechnology and Life Sciences, 120 Flagg Road, Kingston, RI, USA., Garzon JLN; Department of Cell and Molecular Biology, University of Rhode Island, 379 Center for Biotechnology and Life Sciences, 120 Flagg Road, Kingston, RI, USA.; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, 94305, USA., Howlett NG; Department of Cell and Molecular Biology, University of Rhode Island, 379 Center for Biotechnology and Life Sciences, 120 Flagg Road, Kingston, RI, USA. nhowlett@uri.edu.
Jazyk: angličtina
Zdroj: Functional & integrative genomics [Funct Integr Genomics] 2024 Oct 04; Vol. 24 (5), pp. 180. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1007/s10142-024-01453-5
Abstrakt: Fanconi anemia (FA) is a rare genetic disease characterized by congenital abnormalities and increased risk for bone marrow failure and cancer. Central nervous system defects, including acute and irreversible loss of neurological function and white matter lesions with calcifications, have become increasingly recognized among FA patients, and are collectively referred to as Fanconi Anemia Neurological Syndrome or FANS. The molecular etiology of FANS is poorly understood. In this study, we have used a functional integrative genomics approach to further define the function of the FANCD2 protein and FA pathway. Combined analysis of new and existing FANCD2 ChIP-seq datasets demonstrates that FANCD2 binds nonrandomly throughout the genome with binding enriched at transcription start sites and in broad regions spanning protein-coding gene bodies. FANCD2 demonstrates a strong preference for large neural genes involved in neuronal differentiation, synapse function, and cell adhesion, with many of these genes implicated in neurodevelopmental and neuropsychiatric disorders. Furthermore, FANCD2 binds to regions of the genome that replicate late, undergo mitotic DNA synthesis (MiDAS) under conditions of replication stress, and are hotspots for copy number variation. Our analysis describes an important targeted role for FANCD2 and the FA pathway in the maintenance of large neural gene stability.
(© 2024. The Author(s).)
Databáze: MEDLINE
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