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Nuclear receptor corepressors in intellectual disability and autism

Molecular Psychiatry volume 25, pages 2220–2236 (2020)Cite this article

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Abstract

Autism spectrum disorder (ASD) is characterized by neurocognitive dysfunctions, such as impaired social interaction and language learning. Gene–environment interactions have a pivotal role in ASD pathogenesis. Nuclear receptor corepressors (NCORs) are transcription co-regulators physically associated with histone deacetylases (HDACs) and many known players in ASD etiology such as transducin β-like 1 X-linked receptor 1 and methyl-CpG binding protein 2. The epigenome-modifying NCOR complex is sensitive to many ASD risk factors, including HDAC inhibitor valproic acid and a variety of endocrine factors, xenobiotic chemicals, or metabolites that can directly bind to multiple nuclear receptors. Here, we review recent studies of NCORs in neurocognition using animal models and human genetics approaches. We discuss functional interplays between NCORs and other known players in ASD etiology. It is conceivable that the NCOR complex may bridge the in utero environmental risk factors of ASD with epigenetic remodeling and can serve as a converging point for many gene–environment interactions in the pathogenesis of ASD and intellectual disability.

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Fig. 1: Illustration of protein–protein interactions between NCOR, TBL1XR1, and MECP2.
Fig. 2: A working model for NCOR functions in the brain.

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Acknowledgements

We are thankful for the following funds that support the laboratories, although none of them directly supports the work described in this review. The funds are NIH grant CA215591, DK111436, and ES027544 (Z.S.), American Diabetes Association grant 1-19-PDF-012 (W.Z.), National Natural Science Foundation of China 31200804 (Y.K.), and the Fundamental Research Funds for the Central Universities 2242019K40122 (Y.K.). We thank John S. Dunn Foundation and Mrs. Clifford Elder White Graham Endowed Research Fund. We are also thankful for the Cardiovascular Research Institute, Dan L Duncan Comprehensive Cancer Center (P30CA125123), Texas Medical Center Digestive Diseases Center (P30DK056338), and the SPORE program in lymphoma (P50 CA126752) at Baylor College of Medicine, and Gulf Coast Center for Precision Environmental Health (P30ES030285).

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  1. Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, China

    Yan Kong

  2. Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA

    Yan Kong, Wenjun Zhou & Zheng Sun

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Kong, Y., Zhou, W. & Sun, Z. Nuclear receptor corepressors in intellectual disability and autism. Mol Psychiatry 25, 2220–2236 (2020). https://doi.org/10.1038/s41380-020-0667-y

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