NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain

Liu, Sanxiong; Aldinger, Kimberly A.; Cheng, Chi Vicky; Kiyama, Takae; Dave, Mitali; McNamara, Hanna K.; Zhao, Wukui; Stafford, James M.; Descostes, Nicolas; Lee, Pedro; Caraffi, Stefano Giuseppe; Ivanovski, Ivan; Errichiello, Edoardo; Zweier, Christiane; Zuffardi, Orsetta; Schneider, Michael; Papavasiliou, Antigone; Perry, Μ. Scott; Humberson, Jennifer; Cho, Megan T.; Weber, Astrid; Swale, Andrew; Badea, Tudor C.; Mao, Chai An; Garavelli, Livia; Dobyns, William B.; Reinberg, Danny

doi:10.1016/j.molcel.2021.09.020

Cited by 34 publications

(43 citation statements)

References 92 publications

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“…The PRC1.5 complex contains the components AUTS2, PCGF5, RING1B, CK2B, and RYBP (Gao et al, 2012;Gao et al, 2014). The binding of AUTS2 to the PRC1.5 complex switches its function to a transcriptional activator by recruiting the histone acetyltransferase EP300 and casein kinase 2 (CK2) (Gao et al, 2014;Liu et al, 2021). Coimmunoprecipitation experiments revealed that RING1B interacts with AUTS2 only in the presence of PCGF5 (Gao et al, 2014), suggesting a bridging function of PCGF5.…”

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

“…Therefore, the recruitment of CK2 to the PRC1.5 complex and the AUTS2-EP300 interaction seem to be responsible for converting the repressive PRC1 function into an activator function (Gao et al, 2014;Monderer-Rothkoff et al, 2021). Recently, de novo pathogenic variants in the HX repeat region of AUTS2 were described in patients with a phenotype overlapping with Rubinstein-Taybi syndrome (Liu et al, 2021). Rubinstein-Taybi syndrome (RSTS, OMIM 180849 and OMIM 613684) is a neurodevelopmental disorder characterized by intellectual disability, autism spectrum disorders, microcephaly, facial dysmorphism, growth retardation, large thumbs and hallux and a variable degree of additional malformations and symptoms (reviewed in Van Gils et al, 2021).…”

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

“…The underlying cause of RSTS are pathogenic variants in EP300 and CREBBP (Petrij et al, 1995;Roelfsema et al, 2005). Interestingly, the AUTS2 variants leading to an RSTS-overlapping phenotype disrupt the binding of AUTS2 to EP300, suggesting that the HX repeat domain is responsible for this interaction (Liu et al, 2021). The binding of AUTS2 to PRC1.3 and the recruitment to chromatin was shown to be directed by the transcription factor nuclear respiratory factor 1 (NRF1).…”

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

“…The binding of AUTS2 to PRC1.3 and the recruitment to chromatin was shown to be directed by the transcription factor nuclear respiratory factor 1 (NRF1). In motor neurons, AUTS2 and NRF1 colocalize at actively transcribed loci, whereby AUTS2 binding requires NRF1, but NRF1 binding is independent of AUTS2 (Liu et al, 2021). Thus, it was suggested that NRF1 recruits AUTS2 in the context of the PRC1.3 complex to genes involved in neuronal differentiation.…”

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

“…Thus, it was suggested that NRF1 recruits AUTS2 in the context of the PRC1.3 complex to genes involved in neuronal differentiation. The transcription of these genes will then be activated by binding of EP300 to the AUTS2 HX repeat domain (Liu et al, 2021).…”

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

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Comparing a Novel Malformation Syndrome Caused by Pathogenic Variants in FBRSL1 to AUTS2 Syndrome

Pauli

Berger

Ufartes

et al. 2021

Front. Cell Dev. Biol.

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Truncating variants in specific exons of Fibrosin-like protein 1 (FBRSL1) were recently reported to cause a novel malformation and intellectual disability syndrome. The clinical spectrum includes microcephaly, facial dysmorphism, cleft palate, skin creases, skeletal anomalies and contractures, postnatal growth retardation, global developmental delay as well as respiratory problems, hearing impairment and heart defects. The function of FBRSL1 is largely unknown, but pathogenic variants in the FBRSL1 paralog Autism Susceptibility Candidate 2 (AUTS2) are causative for an intellectual disability syndrome with microcephaly (AUTS2 syndrome). Some patients with AUTS2 syndrome also show additional symptoms like heart defects and contractures overlapping with the phenotype presented by patients with FBRSL1 mutations. For AUTS2, a dual function, depending on different isoforms, was described and suggested for FBRSL1. Both, nuclear FBRSL1 and AUTS2 are components of the Polycomb subcomplexes PRC1.3 and PRC1.5. These complexes have essential roles in developmental processes, cellular differentiation and proliferation by regulating gene expression via histone modification. In addition, cytoplasmic AUTS2 controls neural development, neuronal migration and neurite extension by regulating the cytoskeleton. Here, we review recent data on FBRSL1 in respect to previously published data on AUTS2 to gain further insights into its molecular function, its role in development as well as its impact on human genetics.

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Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

Section: Auts2 Has Nuclear and Cytoplasmic Functions Which May Be Shared By Fbrsl1mentioning

confidence: 99%

See 3 more Smart Citations

Comparing a Novel Malformation Syndrome Caused by Pathogenic Variants in FBRSL1 to AUTS2 Syndrome

Pauli

Berger

Ufartes

et al. 2021

Front. Cell Dev. Biol.

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Polycomb‐mediated gene regulation in human brain development and neurodevelopmental disorders

Bölicke

Albert

2022

Developmental Neurobiology

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The neocortex is considered the seat of higher cognitive function in humans. It develops from a sheet of neural progenitor cells, most of which eventually give rise to neurons. This process of cell fate determination is controlled by precise temporal and spatial gene expression patterns that in turn are affected by epigenetic mechanisms including Polycomb group (PcG) regulation. PcG proteins assemble in multiprotein complexes and catalyze repressive posttranslational histone modifications. Their association with neurodevelopmental disease and various types of cancer of the central nervous system, as well as observations in mouse models, has implicated these epigenetic modifiers in controlling various stages of cortex development. The precise mechanisms conveying PcG‐associated transcriptional repression remain incompletely understood and are an active field of research. PcG activity appears to be highly context‐specific, raising the question of species‐specific differences in the regulation of neural stem and progenitor regulation. In this review, we will discuss our growing understanding of how PcG regulation affects human cortex development, based on studies in murine model systems, but focusing mostly on findings obtained from examining impaired PcG activity in the context of human neurodevelopmental disorders and cancer. Furthermore, we will highlight relevant experimental approaches for functional investigations of PcG regulation in human cortex development.

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H2A monoubiquitination: insights from human genetics and animal models

et al. 2023

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NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain

Cited by 34 publications

References 92 publications

Comparing a Novel Malformation Syndrome Caused by Pathogenic Variants in FBRSL1 to AUTS2 Syndrome

Comparing a Novel Malformation Syndrome Caused by Pathogenic Variants in FBRSL1 to AUTS2 Syndrome

Polycomb‐mediated gene regulation in human brain development and neurodevelopmental disorders

H2A monoubiquitination: insights from human genetics and animal models

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