From neural development to cognition: unexpected roles for chromatin
TLDR
Interestingly, mutations in EZH2 and certain BAF complex components have roles in both neurodevelopmental disorders and cancer, and overlapping point mutations are suggesting functionally important residues and domains.Abstract:
Recent genome-sequencing studies in human neurodevelopmental and psychiatric disorders have revealed mutations in chromatin-modifying enzymes, such as chromatin remodellers and histone-modifying enzymes. Such studies are improving our understanding of the roles of these modifiers in human neurodevelopment, and this article discusses the emerging roles for several of these enzymes in development and disease.read more
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Journal ArticleDOI
Heterochromatin remodeling by CDK12 contributes to learning in Drosophila.
Li-Xia Pan,Wenbing Xie,Kai Le Li,Zhihao Yang,Jiang Xu,Wen-Hao Zhang,Lu Ping Liu,Xingjie Ren,Zhimin He,Junyu Wu,Jin Sun,Hui Min Wei,Da-Liang Wang,Wei Xie,Wei Li,Jian-Quan Ni,Fang-Lin Sun,Fang-Lin Sun +17 more
TL;DR: It is shown that cyclin-dependent kinase 12 (CDK12), a transcription elongation-associated RNA polymerase II (RNAPII) kinase, antagonizes heterochromatin enrichment in Drosophila chromosomes, which defines a previously unidentified role of CDK12 in controlling the epigenetic transition between euchromatin and heterochromaatin and suggest a chromatin regulatory mechanism in neuronal behaviors.
Journal ArticleDOI
Connecting the dots: Overlaps between autism and cancer suggest possible common mechanisms regarding signaling pathways related to metabolic alterations.
Ya Wen,Martha R. Herbert +1 more
TL;DR: It is hypothesize that further studies focusing on illuminating the relationships between ASDs and cancer, specifically with regard to signaling pathways that regulate metabolic activities, could help shed new insight on these conditions and develop treatment strategies that, by targeting underlying mechanisms, may be more efficient and effective for both conditions.
Journal ArticleDOI
Reprogramming human fibroblasts to neurons by recapitulating an essential microRNA-chromatin switch.
TL;DR: The development of the vertebrate nervous system requires a switch of ATP-dependent chromatin remodeling mechanisms, which occurs by substituting subunits within these complexes near cell cycle exit, which plays genetically dominant roles in several human neurologic diseases.
Journal ArticleDOI
The role of ARID1B, a BAF chromatin remodeling complex subunit, in neural development and behavior.
Jeffrey J. Moffat,Eui-Man Jung,Minhan Ka,Amanda L. Smith,Byeong Tak Jeon,Gijs W. E. Santen,Woo Yang Kim +6 more
TL;DR: The utility of the Arid1b heterozygous mouse model in neurodevelopmental and psychiatric research is discussed and some of the opportunities and potential challenges in developing translational applications for humans are discussed.
References
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Journal ArticleDOI
An integrated encyclopedia of DNA elements in the human genome
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
Translating the Histone Code
Thomas Jenuwein,C. David Allis +1 more
TL;DR: It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
Journal ArticleDOI
Functions of DNA methylation: islands, start sites, gene bodies and beyond
TL;DR: Improved genome-scale mapping of methylation allows us to evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences.
Journal ArticleDOI
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
Ruthie E. Amir,Ignatia B. Van den Veyver,Mimi Wan,Charles Q. Tran,Uta Francke,Huda Y. Zoghbi +5 more
TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
Journal ArticleDOI
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Tarjei S. Mikkelsen,Manching Ku,Manching Ku,David B. Jaffe,Biju Issac,Biju Issac,Erez Lieberman Aiden,Erez Lieberman Aiden,Georgia Giannoukos,Pablo Alvarez,William Brockman,Tae Kyung Kim,Richard Koche,Richard Koche,Richard Koche,William Lee,Eric M. Mendenhall,Eric M. Mendenhall,Aisling O'Donovan,Aviva Presser,Carsten Russ,Xiaohui Xie,Alexander Meissner,Marius Wernig,Rudolf Jaenisch,Chad Nusbaum,Eric S. Lander,Eric S. Lander,Bradley E. Bernstein,Bradley E. Bernstein +29 more
TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
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