Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked gene PRODH.
Maria Suntsova,Elena Gogvadze,S. V. Salozhin,Nurshat Gaifullin,Fedor M. Eroshkin,Sergey E. Dmitriev,Natalia Y. Martynova,Kirill Kulikov,Galina Malakhova,Gulnur Tukhbatova,Alexey P. Bolshakov,Dmitry Ghilarov,Andrew Garazha,Alexander Aliper,Charles R. Cantor,Yuri Solokhin,Sergey A. Roumiantsev,Pavel M. Balaban,Alex Zhavoronkov,Anton Buzdin +19 more
TLDR
A systematic, whole-genome analysis of enhancer activity of human-specific endogenous retroviral inserts (hsERVs) identified an element, hsERVPRODH, that acts as a tissue-specific enhancer for the PRODH gene, which is required for proper CNS functioning and is proposed to have contributed to human CNS evolution.Abstract:
Using a systematic, whole-genome analysis of enhancer activity of human-specific endogenous retroviral inserts (hsERVs), we identified an element, hsERVPRODH, that acts as a tissue-specific enhancer for the PRODH gene, which is required for proper CNS functioning. PRODH is one of the candidate genes for susceptibility to schizophrenia and other neurological disorders. It codes for a proline dehydrogenase enzyme, which catalyses the first step of proline catabolism and most likely is involved in neuromediator synthesis in the CNS. We investigated the mechanisms that regulate hsERVPRODH enhancer activity. We showed that the hsERVPRODH enhancer and the internal CpG island of PRODH synergistically activate its promoter. The enhancer activity of hsERVPRODH is regulated by methylation, and in an undermethylated state it can up-regulate PRODH expression in the hippocampus. The mechanism of hsERVPRODH enhancer activity involves the binding of the transcription factor SOX2, whch is preferentially expressed in hippocampus. We propose that the interaction of hsERVPRODH and PRODH may have contributed to human CNS evolution.read more
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Schizophrenia risk from complex variation of complement component 4
Aswin Sekar,Aswin Sekar,Allison R. Bialas,Heather de Rivera,Heather de Rivera,Avery Davis,Avery Davis,Timothy R. Hammond,Nolan Kamitaki,Nolan Kamitaki,Katherine Tooley,Katherine Tooley,Jessy Presumey,Matthew A. Baum,Vanessa Van Doren,Giulio Genovese,Giulio Genovese,Samuel A. Rose,Robert E. Handsaker,Robert E. Handsaker,Mark J. Daly,Mark J. Daly,Michael C. Carroll,Beth Stevens,Beth Stevens,Steven A. McCarroll,Steven A. McCarroll +26 more
TL;DR: It is found that many structurally diverse alleles of the complement component 4 (C4) genes generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C 4A.
Journal ArticleDOI
Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs
Julien Pontis,Evarist Planet,Sandra Offner,Priscilla Turelli,Julien Duc,Alexandre Coudray,Thorold W. Theunissen,Rudolf Jaenisch,Didier Trono +8 more
TL;DR: By controlling the transcriptional impact of TEs during embryogenesis, KZFPs facilitate their genome-wide incorporation into transcriptional networks, thereby contributing to human genome regulation.
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Proline metabolism and cancer: emerging links to glutamine and collagen
TL;DR: Mechanisms by which the proline regulatory axis modulates the cancer phenotype are being revealed.
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Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses
TL;DR: It is increasingly clear that proline metabolism plays an important role in metabolic reprogramming, not only in cancer but also in related fields such as aging, senescence, and development.
Journal ArticleDOI
Human endogenous retrovirus-K (HML-2): a comprehensive review.
TL;DR: The discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis are discussed and different therapeutic approaches being considered to target these viruses are presented.
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