Similar Datasets
Project description:During postnatal development the DNA methyltransferase DNMT3A deposits high levels of nonCG cytosine methylation in neurons. This unique methylation is critical for transcriptional regulation in the mature mammalian brain, and loss of this mark is implicated in DNMT3Aassociated neurodevelopmental disorders (NDDs). The mechanisms determining genomic nonCG methylation profiles are not well defined however, and it is unknown if this pathway is disrupted in additional NDDs. Here we show that genome topology and gene-expression converge to shape Histone H3 lysine 36 dimethylation (H3K36me2) profiles, which in turn recruit DNMT3A and pattern neuronal non-CG methylation. Brain-specific deletion of NSD1, the H3K36 methyltransferase mutated in the NDD Sotos syndrome, disrupts megabase-scale H3K36me2 patterns, causing alterations in non-CG methylation and transcription that overlap models of DNMT3A disorders. Our findings indicate that H3K36me2 deposited by NSD1 is an important determinant of neuronal non-CG DNA methylation and implicates disruption of this methylation in Sotos syndrome.
2023-07-07 | GSE212844 | GEO
Project description:During postnatal development the DNA methyltransferase DNMT3A deposits high levels of nonCG cytosine methylation in neurons. This unique methylation is critical for transcriptional regulation in the mature mammalian brain, and loss of this mark is implicated in DNMT3Aassociated neurodevelopmental disorders (NDDs). The mechanisms determining genomic nonCG methylation profiles are not well defined however, and it is unknown if this pathway is disrupted in additional NDDs. Here we show that genome topology and gene-expression converge to shape Histone H3 lysine 36 dimethylation (H3K36me2) profiles, which in turn recruit DNMT3A and pattern neuronal non-CG methylation. Brain-specific deletion of NSD1, the H3K36 methyltransferase mutated in the NDD Sotos syndrome, disrupts megabase-scale H3K36me2 patterns, causing alterations in non-CG methylation and transcription that overlap models of DNMT3A disorders. Our findings indicate that H3K36me2 deposited by NSD1 is an important determinant of neuronal non-CG DNA methylation and implicates disruption of this methylation in Sotos syndrome.
2023-07-07 | GSE212843 | GEO
Project description:During postnatal development the DNA methyltransferase DNMT3A deposits high levels of nonCG cytosine methylation in neurons. This unique methylation is critical for transcriptional regulation in the mature mammalian brain, and loss of this mark is implicated in DNMT3Aassociated neurodevelopmental disorders (NDDs). The mechanisms determining genomic nonCG methylation profiles are not well defined however, and it is unknown if this pathway is disrupted in additional NDDs. Here we show that genome topology and gene-expression converge to shape Histone H3 lysine 36 dimethylation (H3K36me2) profiles, which in turn recruit DNMT3A and pattern neuronal non-CG methylation. Brain-specific deletion of NSD1, the H3K36 methyltransferase mutated in the NDD Sotos syndrome, disrupts megabase-scale H3K36me2 patterns, causing alterations in non-CG methylation and transcription that overlap models of DNMT3A disorders. Our findings indicate that H3K36me2 deposited by NSD1 is an important determinant of neuronal non-CG DNA methylation and implicates disruption of this methylation in Sotos syndrome.
2023-07-07 | GSE212846 | GEO
Project description:During postnatal development the DNA methyltransferase DNMT3A deposits high levels of nonCG cytosine methylation in neurons. This unique methylation is critical for transcriptional regulation in the mature mammalian brain, and loss of this mark is implicated in DNMT3Aassociated neurodevelopmental disorders (NDDs). The mechanisms determining genomic nonCG methylation profiles are not well defined however, and it is unknown if this pathway is disrupted in additional NDDs. Here we show that genome topology and gene-expression converge to shape Histone H3 lysine 36 dimethylation (H3K36me2) profiles, which in turn recruit DNMT3A and pattern neuronal non-CG methylation. Brain-specific deletion of NSD1, the H3K36 methyltransferase mutated in the NDD Sotos syndrome, disrupts megabase-scale H3K36me2 patterns, causing alterations in non-CG methylation and transcription that overlap models of DNMT3A disorders. Our findings indicate that H3K36me2 deposited by NSD1 is an important determinant of neuronal non-CG DNA methylation and implicates disruption of this methylation in Sotos syndrome.
2023-07-07 | GSE212845 | GEO
Project description:During postnatal development the DNA methyltransferase DNMT3A deposits high levels of nonCG cytosine methylation in neurons. This unique methylation is critical for transcriptional regulation in the mature mammalian brain, and loss of this mark is implicated in DNMT3Aassociated neurodevelopmental disorders (NDDs). The mechanisms determining genomic nonCG methylation profiles are not well defined however, and it is unknown if this pathway is disrupted in additional NDDs. Here we show that genome topology and gene-expression converge to shape Histone H3 lysine 36 dimethylation (H3K36me2) profiles, which in turn recruit DNMT3A and pattern neuronal non-CG methylation. Brain-specific deletion of NSD1, the H3K36 methyltransferase mutated in the NDD Sotos syndrome, disrupts megabase-scale H3K36me2 patterns, causing alterations in non-CG methylation and transcription that overlap models of DNMT3A disorders. Our findings indicate that H3K36me2 deposited by NSD1 is an important determinant of neuronal non-CG DNA methylation and implicates disruption of this methylation in Sotos syndrome.
2023-07-07 | GSE212842 | GEO
Project description:During postnatal development the DNA methyltransferase DNMT3A deposits high levels of nonCG cytosine methylation in neurons. This unique methylation is critical for transcriptional regulation in the mature mammalian brain, and loss of this mark is implicated in DNMT3Aassociated neurodevelopmental disorders (NDDs). The mechanisms determining genomic nonCG methylation profiles are not well defined however, and it is unknown if this pathway is disrupted in additional NDDs. Here we show that genome topology and gene-expression converge to shape Histone H3 lysine 36 dimethylation (H3K36me2) profiles, which in turn recruit DNMT3A and pattern neuronal non-CG methylation. Brain-specific deletion of NSD1, the H3K36 methyltransferase mutated in the NDD Sotos syndrome, disrupts megabase-scale H3K36me2 patterns, causing alterations in non-CG methylation and transcription that overlap models of DNMT3A disorders. Our findings indicate that H3K36me2 deposited by NSD1 is an important determinant of neuronal non-CG DNA methylation and implicates disruption of this methylation in Sotos syndrome.
2023-07-07 | GSE212841 | GEO
Project description:NSD1 deposits Histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons
| PRJNA877631 | ENA
Project description:NSD1 deposits Histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons [ChIP Rx]
| PRJNA877638 | ENA
Project description:NSD1 deposits Histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons [RNA-seq]
| PRJNA877637 | ENA
Project description:UnlabelledNumerous studies in multiple systems support that histone H3 lysine 36 dimethylation (H3K36me2) is associated with transcriptional activation; however, the underlying mechanisms are not well defined. Here, we show that the H3K36me2 chromatin mark written by the ASH1L histone methyltransferase is preferentially bound in vivo by LEDGF, a mixed-lineage leukemia (MLL)-associated protein that colocalizes with MLL, ASH1L, and H3K36me2 on chromatin genome wide. Furthermore, ASH1L facilitates recruitment of LEDGF and wild-type MLL proteins to chromatin at key leukemia target genes and is a crucial regulator of MLL-dependent transcription and leukemic transformation. Conversely, KDM2A, an H3K36me2 demethylase and Polycomb group silencing protein, antagonizes MLL-associated leukemogenesis. Our studies are the first to provide a basic mechanistic insight into epigenetic interactions wherein placement, interpretation, and removal of H3K36me2 contribute to the regulation of gene expression and MLL leukemia, and suggest ASH1L as a novel target for therapeutic intervention.SignificanceEpigenetic regulators play vital roles in cancer pathogenesis and represent a new frontier in therapeutic targeting. Our studies provide basic mechanistic insight into the role of H3K36me2 in transcription activation and MLL leukemia pathogenesis and implicate ASH1L histone methyltransferase as a promising target for novel molecular therapy. Cancer Discov; 6(7); 770-83. ©2016 AACR.See related commentary by Balbach and Orkin, p. 700This article is highlighted in the In This Issue feature, p. 681.
| S-EPMC4930721 | biostudies-literature