SETD5 Regulates Chromatin Methylation State and Preserves Global Transcriptional Fidelity during Brain Development and Neuronal Wiring

Sessa, Alessandro; Fagnocchi, Luca; Mastrototaro, Giuseppina; Massimino, Luca; Zaghi, Mattia; Indrigo, Marzia; Cattaneo, Stefano; Martini, Davide; Gabellini, Chiara; Pucci, C; Fasciani, Alessandra; Belli, Romina; Taverna, Stefano; Andreazzoli, Massimiliano; Zippo, Alessio; Broccoli, Vania

doi:10.1016/j.neuron.2019.07.013

Cited by 89 publications

(122 citation statements)

References 92 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…In addition, specific hPTMS are strongly associated with different splicing types. H3K36me3 marks splicing related exons as shown in studies profiling H3K36me3 enrichment as lower in alternative splicing exons than constitutive exons (Hu et al, 2017;Kolasinska-Zwierz et al, 2009;Luco et al, 2010;Sessa et al, 2019;Wilhelm et al, 2011). H3K36me3 also facilitates efficient mRNA splicing through recruitment of an "adapter protein" to stabilize splice factors and regulate proper co-transcriptional splicesome assembly (Leung et al, 2019).…”

Section: Discussionmentioning

confidence: 98%

“…We next sought to build on previous evidence that links Set2-dependent H3K36me3 to alternative splicing (De Almeida et al, 2011;Luco et al, 2010;Pajoro et al, 2017;Sessa et al, 2019;Xu et al, 2017;Yuan et al, 2017;Zhou et al, 2012). Although in higher eukaryotes multiple H3K36 methyltransferases catalyze H3K36me1 and H3K36me2, the yeast Set2 homolog is specific to H3K36me3 (McDaniel and Strahl, 2017;Sorenson et al, 2016;Strahl et al, 2002).…”

Section: Set2 Overexpression In Nac Regulated Alternative Splicing VImentioning

confidence: 99%

See 1 more Smart Citation

Chromatin-mediated alternative splicing regulates cocaine reward behavior

Lombroso

Carpenter

et al. 2019

Preprint

View full text Add to dashboard Cite

Alternative splicing is a key mechanism for neuronal gene regulation, and is grossly altered in mouse brain reward regions following investigator-administered cocaine. It is well established that cocaine epigenetically regulates transcription, yet mechanism(s) by which cocaine-induced epigenetic modifications regulate alternative splicing is largely unexplored. Our group and others have previously identified the histone modification, H3K36me3, as a putative splicing regulator. However, it has not yet been possible to establish the direct causal relevance of this modification to alternative splicing in brain or any other context. We found that mouse cocaine self-administration caused widespread alternative splicing, concomitant with enrichment of H3K36me3 at splice junctions. Differentially spliced genes were enriched in the motif for splice factor, Srsf11, which was both differentially spliced and enriched in H3K36me3. Epigenetic editing led us to conclude that H3K36me3 functions directly in alternative splicing of Srsf11, and that Set2 mediated H3K36me3 bidirectionally regulates cocaine intake.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Set2 Overexpression In Nac Regulated Alternative Splicing VImentioning

confidence: 99%

Chromatin-mediated alternative splicing regulates cocaine reward behavior

Lombroso

Carpenter

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Methylation of histone complexes is another topic of interest, as many ASD genes are linked to chromatin remodeling. For example, SETD5 happloinsufficiency revealed that SETD5 methylates histones directly, suggesting an important role of H3K63 methylation, which in turn regulates RNA elongation and processing [56]. Together, these studies emphasize how important PTMs are for protein regulation and function.…”

Section: Identifying and Quantifying Post-translation Modificationsmentioning

confidence: 97%

Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders

Murtaza

Singh

2020

Molecular Autism

View full text Add to dashboard Cite

Proteomics is the large-scale study of the total protein content and their overall function within a cell through multiple facets of research. Advancements in proteomic methods have moved past the simple quantification of proteins to the identification of post-translational modifications (PTMs) and the ability to probe interactions between these proteins, spatially and temporally. Increased sensitivity and resolution of mass spectrometers and sample preparation protocols have drastically reduced the large amount of cells required and the experimental variability that had previously hindered its use in studying human neurological disorders. Proteomics offers a new perspective to study the altered molecular pathways and networks that are associated with autism spectrum disorders (ASD). The differences between the transcriptome and proteome, combined with the various types of post-translation modifications that regulate protein function and localization, highlight a novel level of research that has not been appropriately investigated. In this review, we will discuss strategies using proteomics to study ASD and other neurological disorders, with a focus on how these approaches can be combined with induced pluripotent stem cell (iPSC) studies. Proteomic analysis of iPSC-derived neurons have already been used to measure changes in the proteome caused by patient mutations, analyze changes in PTMs that resulted in altered biological pathways, and identify potential biomarkers. Further advancements in both proteomic techniques and human iPSC differentiation protocols will continue to push the field towards better understanding ASD disease pathophysiology. Proteomics using iPSC-derived neurons from individuals with ASD offers a window for observing the altered proteome, which is necessary in the future development of therapeutics against specific targets. Autism spectrum disorders

show abstract

“…Chromatin remodelers AT-rich interaction domain 1B (Arid1b) and chromodomain helicase DNA-binding protein 8 (Chd8) [216][217][218][219][220][221], histone methyltransferase euchromatic histone lysine methyltransferase 1 (Ehmt1) [222,223], and transcriptional regulators Foxp1 and Foxp2 [224][225][226][227][228][229][230][231] were targeted to investigate ASD-like behavioral phenotypes in mutated mice. SET domain-containing 5 (Setd5) was suggested as one of the histone methyltransferase candidates [232], but methyltransferase activity of Setd5 was not accepted by the majority of other researchers [233,234].…”

Section: Dna Methylationmentioning

confidence: 99%

Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder

Yoon

Choi

Lee

et al. 2020

JCM

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by difficulties in social interaction, language development delays, repeated body movements, and markedly deteriorated activities and interests. Environmental factors, such as viral infection, parental age, and zinc deficiency, can be plausible contributors to ASD susceptibility. As ASD is highly heritable, genetic risk factors involved in neurodevelopment, neural communication, and social interaction provide important clues in explaining the etiology of ASD. Accumulated evidence also shows an important role of epigenetic factors, such as DNA methylation, histone modification, and noncoding RNA, in ASD etiology. In this review, we compiled the research published to date and described the genetic and epigenetic epidemiology together with environmental risk factors underlying the etiology of the different phenotypes of ASD.

show abstract

SETD5 Regulates Chromatin Methylation State and Preserves Global Transcriptional Fidelity during Brain Development and Neuronal Wiring

Cited by 89 publications

References 92 publications

Chromatin-mediated alternative splicing regulates cocaine reward behavior

Chromatin-mediated alternative splicing regulates cocaine reward behavior

Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders

Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder

Contact Info

Product

Resources

About