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
Citations
More filters
Journal ArticleDOI
Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration
Sima Khazaei,Carol C.L. Chen,Augusto Faria Andrade,Nisha Kabir,Pariya Azarafshar,Shahir M. Morcos,Josiane Alves França,Mariana Lopes,Peder Lund,Geoffroy Danieau,Samantha Worme,Lata Adnani,Nadine Nzirorera,Xiao Chen,Gayathri Yogarajah,Caterina Russo,Michele Zeinieh,Cassandra J. Wong,Laura Bryant,Steven Hebert,Bethany Tong,Tianna S. Sihota,Damien Faury,Evan Puligandla,Wajih Jawhar,Veronica Sandy,Mitra Cowan,Emily M. Nakada,Loydie A. Jerome-Majewska,Benjamin Ellezam,Carolina Cavaliéri Gomes,Jonas Denecke,Davor Lessel,Marie T. McDonald,Carolyn Pizoli,Kathryn R. Taylor,Benjamin T. Cocanougher,Elizabeth J. Bhoj,Anne-Claude Gingras,Benjamin A. Garcia,Chao Lu,Eric I. Campos,Claudia L. Kleinman,Livia Garzia,Nada Jabado +44 more
TL;DR: In this article , H3.3G34R/V/W mutants exhibited microcephaly and neurodegeneration, with abnormal accumulation of disease-associated microglia and concurrent neuronal depletion.
Journal ArticleDOI
RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome.
Léo Mietton,Nicolas Lebrun,Irina Giurgea,Alice Goldenberg,Benjamin Saintpierre,Benjamin Saintpierre,Benjamin Saintpierre,Juliette Hamroune,Juliette Hamroune,Juliette Hamroune,Alexandra Afenjar,Pierre Billuart,Thierry Bienvenu +12 more
TL;DR: Analysis of the pathways and biological functions significantly deregulated between patients with WSS and healthy individuals revealed a number of processes predicted to be altered that are relevant for hypertrichosis and intellectual disability, the cardinal signs of this disease.
Journal ArticleDOI
ACTL6A suppresses p21Cip1 tumor suppressor expression to maintain an aggressive mesothelioma cancer cell phenotype.
Suruchi Shrestha,Gautam Adhikary,Warren Naselsky,Wen Xu,Joseph S. Friedberg,Richard L. Eckert +5 more
TL;DR: In this paper, it was shown that ACTL6A inhibition of p21Cip1 promoter activity is required for maintaining the aggressive mesothelioma cancer cell phenotype.
Journal ArticleDOI
Testicular sex cord-stromal tumor in a boy with 2q37 deletion syndrome
Yasunari Sakai,Ryota Souzaki,Hidetaka Yamamoto,Yuki Matsushita,Hazumu Nagata,Yoshito Ishizaki,Hiroyuki Torisu,Hiroyuki Torisu,Yoshinao Oda,Tomoaki Taguchi,Chad A. Shaw,Toshiro Hara +11 more
TL;DR: The data provide evidence that the phenotypic variations and unusual complications of 2q37 deletion syndrome are not simply explained by the deleted size or genes located at 2q 37, but that external CNVs may account at least in part for their variant phenotypes.
Journal ArticleDOI
Post-transcriptional control of a stemness signature by RNA-binding protein MEX3A regulates murine adult neurogenesis
Ana Domingo-Muelas,Pere Duart-Abadia,José Manuel Morante-Redolat,Antonio Jordán-Pla,German Belenguer,Jaime Fabra-Beser,Lucía Paniagua-Herranz,Ana Perez-Villalba,Adrián Álvarez-Varela,Francisco M. Barriga,Cristina Gil-Sanz,Felipe Ortega,Eduard Batlle,Isabel Fariñas +13 more
TL;DR: In this article , the RNA-binding protein MEX3A was identified as a post-transcriptional regulator of a set of stemness associated transcripts at critical transitions in the subependymal neurogenic lineage.
References
More filters
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.
Related Papers (5)
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
Brian J. O'Roak,Laura Vives,Santhosh Girirajan,Emre Karakoc,Niklas Krumm,Bradley P. Coe,Roie Levy,Arthur Ko,Choli Lee,Joshua D. Smith,Emily H. Turner,Ian B. Stanaway,Benjamin Vernot,Maika Malig,Carl Baker,Beau Reilly,Joshua M. Akey,Elhanan Borenstein,Elhanan Borenstein,Mark J. Rieder,Deborah A. Nickerson,Raphael Bernier,Jay Shendure,Evan E. Eichler,Evan E. Eichler +24 more
Patterns and rates of exonic de novo mutations in autism spectrum disorders
Benjamin M. Neale,Yan Kou,Li Liu,Avi Ma'ayan,Kaitlin E. Samocha,Kaitlin E. Samocha,Aniko Sabo,Chiao-Feng Lin,Christine Stevens,Li-San Wang,Vladimir Makarov,Paz Polak,Paz Polak,Seungtai Yoon,Jared Maguire,Emily L. Crawford,Nicholas G. Campbell,Evan T. Geller,Otto Valladares,Chad M. Schafer,Han Liu,Tuo Zhao,Guiqing Cai,Jayon Lihm,Ruth Dannenfelser,Omar Jabado,Zuleyma Peralta,Uma Nagaswamy,Donna M. Muzny,Jeffrey G. Reid,Irene Newsham,Yuanqing Wu,Lora Lewis,Yi Han,Benjamin F. Voight,Benjamin F. Voight,Elaine T. Lim,Elaine T. Lim,Elizabeth J. Rossin,Elizabeth J. Rossin,Andrew Kirby,Andrew Kirby,Jason Flannick,Menachem Fromer,Menachem Fromer,Khalid Shakir,Timothy Fennell,Kiran V. Garimella,Eric Banks,Ryan Poplin,Stacey Gabriel,Mark A. DePristo,Jack R. Wimbish,Braden E. Boone,Shawn Levy,Catalina Betancur,Shamil R. Sunyaev,Shamil R. Sunyaev,Eric Boerwinkle,Eric Boerwinkle,Joseph D. Buxbaum,Edwin H. Cook,Bernie Devlin,Richard A. Gibbs,Kathryn Roeder,Gerard D. Schellenberg,James S. Sutcliffe,Mark J. Daly,Mark J. Daly +68 more
Synaptic, transcriptional and chromatin genes disrupted in autism
Silvia De Rubeis,Xin-Xin He,Arthur P. Goldberg,Christopher S. Poultney,Kaitlin E. Samocha,A. Ercument Cicek,Yan Kou,Li Liu,Menachem Fromer,Menachem Fromer,R. Susan Walker,Tarjinder Singh,Lambertus Klei,Jack A. Kosmicki,Shih-Chen Fu,Branko Aleksic,Monica Biscaldi,Patrick Bolton,Jessica M. Brownfeld,Jinlu Cai,Nicholas G. Campbell,Angel Carracedo,Angel Carracedo,Maria H. Chahrour,Andreas G. Chiocchetti,Hilary Coon,Emily L. Crawford,Lucy Crooks,Sarah Curran,Geraldine Dawson,Eftichia Duketis,Bridget A. Fernandez,Louise Gallagher,Evan T. Geller,Stephen J. Guter,R. Sean Hill,R. Sean Hill,Iuliana Ionita-Laza,Patricia Jiménez González,Helena Kilpinen,Sabine M. Klauck,Alexander Kolevzon,Irene Lee,Jing Lei,Terho Lehtimäki,Chiao-Feng Lin,Avi Ma'ayan,Christian R. Marshall,Alison L. McInnes,Benjamin M. Neale,Michael John Owen,Norio Ozaki,Mara Parellada,Jeremy R. Parr,Shaun Purcell,Kaija Puura,Deepthi Rajagopalan,Karola Rehnström,Abraham Reichenberg,Aniko Sabo,Michael Sachse,Stephen Sanders,Chad M. Schafer,Martin Schulte-Rüther,David Skuse,David Skuse,Christine Stevens,Peter Szatmari,Kristiina Tammimies,Otto Valladares,Annette Voran,Li-San Wang,Lauren A. Weiss,A. Jeremy Willsey,Timothy W. Yu,Timothy W. Yu,Ryan K. C. Yuen,Edwin H. Cook,Christine M. Freitag,Michael Gill,Christina M. Hultman,Thomas Lehner,Aarno Palotie,Aarno Palotie,Aarno Palotie,Gerard D. Schellenberg,Pamela Sklar,Matthew W. State,James S. Sutcliffe,Christopher A. Walsh,Christopher A. Walsh,Stephen W. Scherer,Michael E. Zwick,Jeffrey C. Barrett,David J. Cutler,Kathryn Roeder,Bernie Devlin,Mark J. Daly,Mark J. Daly,Joseph D. Buxbaum +99 more
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Stephen Sanders,Michael T. Murtha,Abha R. Gupta,John D. Murdoch,Melanie J. Raubeson,A. Jeremy Willsey,A. Gulhan Ercan-Sencicek,Nicholas M. DiLullo,Neelroop N. Parikshak,Jason L. Stein,Michael F. Walker,Gordon T. Ober,Nicole A. Teran,Youeun Song,Paul El-Fishawy,Ryan C. Murtha,Murim Choi,John D. Overton,Robert D. Bjornson,Nicholas Carriero,Kyle A. Meyer,Kaya Bilguvar,Shrikant Mane,Nenad Sestan,Richard P. Lifton,Murat Gunel,Kathryn Roeder,Daniel H. Geschwind,Bernie Devlin,Matthew W. State +29 more
De Novo Gene Disruptions in Children on the Autistic Spectrum
Ivan Iossifov,Michael Ronemus,Dan Levy,Zihua Wang,Inessa Hakker,Julie Rosenbaum,Boris Yamrom,Yoon-ha Lee,Giuseppe Narzisi,Anthony Leotta,Jude Kendall,Ewa A. Grabowska,Beicong Ma,Steven Marks,Linda Rodgers,Asya Stepansky,Jennifer Troge,Peter Andrews,Mitchell A. Bekritsky,Kith Pradhan,Elena Ghiban,Melissa Kramer,Jennifer Parla,Ryan Demeter,Lucinda Fulton,Robert S. Fulton,Vincent Magrini,Kenny Ye,Jennifer C. Darnell,Robert B. Darnell,Robert B. Darnell,Elaine R. Mardis,Richard K. Wilson,Michael C. Schatz,Richard W. McCombie,Michael Wigler +35 more