CTCF barrier breaking by ZFP661 promotes protocadherin diversity in mammalian brains.

Autor:	Jin J; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA., Ralls S; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA., Wu E; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA., Wolf G; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA., Sun MA; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.; Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China., Springer DA; The National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Cosby RL; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA., Senft AD; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA., Macfarlan TS; The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 May 08. Date of Electronic Publication: 2023 May 08.
DOI:	10.1101/2023.05.08.539838
Abstrakt:	Mammalian brains are larger and more densely packed with neurons than reptiles, but the genetic mechanisms underlying the increased connection complexity amongst neurons are unclear. The expression diversity of clustered protocadherins (Pcdhs), which is controlled by CTCF and cohesin, is crucial for proper dendritic arborization and cortical connectivity in vertebrates. Here, we identify a highly-conserved and mammalian-restricted protein, ZFP661, that binds antagonistically at CTCF barriers at the Pcdh locus, preventing CTCF from trapping cohesin. ZFP661 balances the usage of Pcdh isoforms and increases Pcdh expression diversity. Loss of Zfp661 causes cortical dendritic arborization defects and autism-like social deficits in mice. Our study reveals both a novel mechanism that regulates the trapping of cohesin by CTCF and a mammalian adaptation that promoted Pcdh expression diversity to accompany the expanded mammalian brain. Competing Interests: Competing interests: The authors declare that they have no competing interests.
Databáze:	MEDLINE
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