RNA, Long Noncoding

Publication Title: 
Folia Histochemica Et Cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society

The insulin-like growth factor-2 (Igf2)-H19 locus encodes important paternally imprinted genes that govern normal embryonic development. While Igf-2 encodes IGF2, which is an autocrine/paracrine mitogen,† transcription of H19 gives rise to non-coding mRNA that is a precursor of several microRNAs (miRNAs) that negatively affect cell proliferation.

Author(s): 
Ratajczak, Mariusz Z.
Publication Title: 
Molecular Psychiatry

Epigenetic studies of DNA and histone modifications represent a new and important activity in molecular investigations of human disease. Our previous epigenome-wide scan identified numerous DNA methylation differences in post-mortem brain samples from individuals affected with major psychosis. In this article, we present the results of fine mapping DNA methylation differences at the human leukocyte antigen (HLA) complex group 9 gene (HCG9) in bipolar disorder (BPD).

Author(s): 
Kaminsky, Z.
Tochigi, M.
Jia, P.
Pal, M.
Mill, J.
Kwan, A.
Ioshikhes, I.
Vincent, J. B.
Kennedy, J. L.
Strauss, J.
Pai, S.
Wang, S.-C.
Petronis, A.
Publication Title: 
Epigenetics

IGF2 is a paternally expressed imprinted gene with an important role in development and brain function. Allele-specific expression of IGF2 is regulated by DNA methylation at three differentially methylated regions (DMRs) spanning the IGF2/H19 domain on human 11p15.5. We have comprehensively assessed DNA methylation and genotype across the three DMRs and the H19 promoter using tissue from a unique collection of well-characterized and neuropathologically-dissected post-mortem human cerebellum samples (n = 106) and frontal cortex samples (n = 51).

Author(s): 
Pidsley, Ruth
Dempster, Emma
Troakes, Claire
Al-Sarraj, Safa
Mill, Jonathan
Publication Title: 
Molecular Brain

BACKGROUND: Insulin-like growth factor 2 (Igf2) is a paternally expressed imprinted gene regulating fetal growth, playing an integral role in the development of many tissues including the brain. The parent-of-origin specific expression of Igf2 is largely controlled by allele-specific DNA methylation at CTCF-binding sites in the imprinting control region (ICR), located immediately upstream of the neighboring H19 gene. Previously we reported evidence of a negative correlation between DNA methylation in this region and cerebellum weight in humans.

Author(s): 
Pidsley, Ruth
Fernandes, Cathy
Viana, Joana
Paya-Cano, Jose L.
Liu, Lin
Smith, Rebecca G.
Schalkwyk, Leonard C.
Mill, Jonathan
Publication Title: 
PloS One

Changes in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case children born small-for-gestational age (SGA, birth weight <-2SDS) and 471 control children. Fetal growth was assessed with serial ultrasound measurements. Information on birth outcomes was retrieved from medical records.

Author(s): 
Bouwland-Both, Marieke I.
van Mil, Nina H.
Stolk, Lisette
Eilers, Paul H. C.
Verbiest, Michael M. P. J.
Heijmans, Bastiaan T.
Tiemeier, Henning
Hofman, Albert
Steegers, Eric A. P.
Jaddoe, Vincent W. V.
Steegers-Theunissen, Régine P. M.
Publication Title: 
Molecular Psychiatry

Regulatory RNA is emerging as the major architect of cognitive evolution and innovation in the mammalian brain. While the protein machinery has remained largely constant throughout animal evolution, the non protein-coding transcriptome has expanded considerably to provide essential and widespread cellular regulation, partly through directing generic protein function. Both long (long non-coding RNA) and small non-coding RNAs (for example, microRNA) have been demonstrated to be essential for brain development and higher cognitive abilities, and to be involved in psychiatric disease.

Author(s): 
Barry, G.
Publication Title: 
European Journal of Medical Genetics

Schizophrenia (SCZ) is a complex mental disorder contributed by both genetic and epigenetic factors. Long noncoding RNAs (lncRNAs) was recently found playing an important regulatory role in mental disorders. However, little was known about the DNA methylation of lncRNAs, although numerous SCZ studies have been performed on genetic polymorphisms or epigenetic marks in protein coding genes. We presented a comprehensive genome wide DNA methylation study of both protein coding genes and lncRNAs in female patients with paranoid and undifferentiated SCZ.

Author(s): 
Liao, Qi
Wang, Yunliang
Cheng, Jia
Dai, Dongjun
Zhou, Xingyu
Zhang, Yuzheng
Gao, Shugui
Duan, Shiwei
Publication Title: 
Advanced Drug Delivery Reviews

Long non-coding RNAs (lncRNA), a class of non-coding RNA molecules recently identified largely due to the efforts of FANTOM, and later GENCODE and ENCODE consortia, have been a subject of intense investigation in the past decade. Extensive efforts to get deeper understanding of lncRNA biology have yielded evidence of their diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation and epigenetic regulation.

Author(s): 
Khorkova, O.
Hsiao, J.
Wahlestedt, C.
Publication Title: 
Schizophrenia Bulletin

New epigenetic technologies may uncover etiopathogenic mechanisms of major psychosis. In this study, we applied padlock probe-based ultra-deep bisulfite sequencing for fine mapping of modified cytosines of the HLA complex group 9 (nonprotein coding) gene in the postmortem brains of individuals affected with schizophrenia or bipolar disorder and unaffected controls. Significant differences between patients and controls were detected in both CpG and CpH modifications.

Author(s): 
Pal, Mrinal
Ebrahimi, Sasha
Oh, Gabriel
Khare, Tarang
Zhang, Aiping
Kaminsky, Zachary A.
Wang, Sun-Chong
Petronis, Arturas
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Bromodomain and extraterminal (BET) domain proteins have emerged as promising therapeutic targets in glioblastoma and many other cancers. Small molecule inhibitors of BET bromodomain proteins reduce expression of several oncogenes required for Glioblastoma Multiforme (GBM) progression. However, the mechanism through which BET protein inhibition reduces GBM growth is not completely understood.

Author(s): 
Pastori, Chiara
Kapranov, Philipp
Penas, Clara
Peschansky, Veronica
Volmar, Claude-Henry
Sarkaria, Jann N.
Bregy, Amade
Komotar, Ricardo
St Laurent, Georges
Ayad, Nagi G.
Wahlestedt, Claes

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