Conserved Higher-Order Chromatin Regulates NMDA Receptor Gene Expression and Cognition

被引：66

作者：

Bharadwaj, Rahul ^{[1
,2
]}

Peter, Cyril J. ^{[1
,2
]}

Jiang, Yan ^{[1
,2
]}

Roussos, Panos ^{[1
,2
,3
,4
]}

Vogel-Ciernia, Annie ^{[16
]}

Shen, Erica Y. ^{[1
,2
]}

Mitchell, Amanda C. ^{[1
,2
]}

Mao, Wenjie ^{[5
]}

Whittle, Catheryne ^{[5
]}

Dincer, Aslihan ^{[1
,2
]}

Jakovcevski, Mira ^{[9
]}

Pothula, Venu ^{[1
,2
]}

Rasmussen, Theodore P. ^{[7
,8
]}

Giakoumaki, Stella G. ^{[10
,11
]}

Bitsios, Panos ^{[6
,10
]}

Sherif, Ajfar ^{[1
,2
]}

Gardner, Paul D. ^{[5
]}

Ernst, Patricia ^{[12
,13
]}

Ghose, Subroto ^{[14
]}

Sklar, Pamela ^{[1
,2
,3
]}

Haroutunian, Vahram ^{[1
,2
,4
]}

Tamminga, Carol ^{[14
]}

Myers, Richard H. ^{[15
]}

Futai, Kensuke ^{[5
]}

Wood, Marcelo A. ^{[16
]}

Akbarian, Schahram ^{[1
,2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Inst Multiscale Biol, New York, NY 10029 USA

[4] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA

[5] Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA 01604 USA

[6] Fdn Res & Technol Hellas, Inst Comp Sci, Computat Med Lab, Iraklion 71003, Greece

[7] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA

[8] Univ Connecticut, Univ Conn Stem Cell Inst, Storrs, CT 06269 USA

[9] Max Planck Inst Psychiat, D-80804 Munich, Germany

[10] Univ Crete, Dept Psychiat, Iraklion 71003, Greece

[11] Univ Crete, Dept Psychol, Iraklion 71003, Greece

[12] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Genet, Hanover, NH 03755 USA

[13] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Microbiol & Immunol, Hanover, NH 03755 USA

[14] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA

[15] Boston Univ, Dept Neurol, Boston, MA 02118 USA

[16] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA

来源：

NEURON | 2014年 / 84卷 / 05期

关键词：

DE-NOVO MUTATIONS; GENOME-WIDE; SYNAPTIC-TRANSMISSION; SCHIZOPHRENIA RISK; PREFRONTAL CORTEX; ENERGY-METABOLISM; MAMMALIAN GENOMES; ENHANCER FUNCTION; SUBUNIT GENES; CYTOCHROME-C;

D O I：

10.1016/j.neuron.2014.10.032

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Three-dimensional chromosomal conformations regulate transcription by moving enhancers and regulatory elements into spatial proximity with target genes. Here we describe activity-regulated long-range loopings bypassing up to 0.5 Mb of linear genome to modulate NMDA glutamate receptor GRIN2B expression in human and mouse prefrontal cortex. Distal intronic and 3' intergenic loop formations competed with repressor elements to access promoter-proximal sequences, and facilitated expression via a "cargo'' of AP-1 and NRF-1 transcription factors and TALE-based transcriptional activators. Neuronal deletion or overexpression of Kmt2a/Mll1 H3K4-and Kmt1e/Setdb1 H3K9-methyl-transferase was associated with higher-order chromatin changes at distal regulatory Grin2b sequences and impairments in working memory. Genetic polymorphisms and isogenic deletions of loop-bound sequences conferred liability for cognitive performance and decreased GRIN2B expression. Dynamic regulation of chromosomal conformations emerges as a novel layer for transcriptional mechanisms impacting neuronal signaling and cognition.

引用

页码：997 / 1008

页数：12

共 74 条

[1] An atlas of active enhancers across human cell types and tissues [J].

Andersson, Robin ;

Gebhard, Claudia ;

Miguel-Escalada, Irene ;

Hoof, Ilka ;

Bornholdt, Jette ;

Boyd, Mette ;

Chen, Yun ;

Zhao, Xiaobei ;

Schmidl, Christian ;

Suzuki, Takahiro ;

Ntini, Evgenia ;

Arner, Erik ;

Valen, Eivind ;

Li, Kang ;

Schwarzfischer, Lucia ;

Glatz, Dagmar ;

Raithel, Johanna ;

Lilje, Berit ;

Rapin, Nicolas ;

Bagger, Frederik Otzen ;

Jorgensen, Mette ;

Andersen, Peter Refsing ;

Bertin, Nicolas ;

Rackham, Owen ;

Burroughs, A. Maxwell ;

Baillie, J. Kenneth ;

Ishizu, Yuri ;

Shimizu, Yuri ;

Furuhata, Erina ;

Maeda, Shiori ;

Negishi, Yutaka ;

Mungall, Christopher J. ;

Meehan, Terrence F. ;

Lassmann, Timo ;

Itoh, Masayoshi ;

Kawaji, Hideya ;

Kondo, Naoto ;

Kawai, Jun ;

Lennartsson, Andreas ;

Daub, Carsten O. ;

Heutink, Peter ;

Hume, David A. ;

Jensen, Torben Heick ;

Suzuki, Harukazu ;

Hayashizaki, Yoshihide ;

Mueller, Ferenc ;

Forrest, Alistair R. R. ;

Carninci, Piero ;

Rehli, Michael ;

Sandelin, Albin .

NATURE, 2014, 507 (7493) :455-+

[2] Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction [J].

Ayalew, M. ;

Le-Niculescu, H. ;

Levey, D. F. ;

Jain, N. ;

Changala, B. ;

Patel, S. D. ;

Winiger, E. ;

Breier, A. ;

Shekhar, A. ;

Amdur, R. ;

Koller, D. ;

Nurnberger, J. I. ;

Corvin, A. ;

Geyer, M. ;

Tsuang, M. T. ;

Salomon, D. ;

Schork, N. J. ;

Fanous, A. H. ;

O'Donovan, M. C. ;

Niculescu, A. B. .

MOLECULAR PSYCHIATRY, 2012, 17 (09) :887-905

[3] EXPRESSION OF A BETA-GLOBIN GENE IS ENHANCED BY REMOTE SV40 DNA-SEQUENCES [J].

BANERJI, J ;

RUSCONI, S ;

SCHAFFNER, W .

CELL, 1981, 27 (02) :299-308

[4] Toward controlling gene expression at will:: Specific regulation of the erbB-2/HER-2 promoter by using polydactyl zinc finger proteins constructed from modular building blocks [J].

Beerli, RR ;

Segal, DJ ;

Dreier, B ;

Barbas, CF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14628-14633

[5] Conserved Chromosome 2q31 Conformations Are Associated with Transcriptional Regulation of GAD1 GABA Synthesis Enzyme and Altered in Prefrontal Cortex of Subjects with Schizophrenia [J].

Bharadwaj, Rahul ;

Jiang, Yan ;

Mao, Wenjie ;

Jakovcevski, Mira ;

Dincer, Aslihan ;

Krueger, Winfried ;

Garbett, Krassimira ;

Whittle, Catheryne ;

Tushir, Jogender Singh ;

Liu, Jia ;

Sequeira, Adolfo ;

Vawter, Marquis P. ;

Gardner, Paul D. ;

Casaccia, Patrizia ;

Rasmussen, Theodore ;

Bunney, William E., Jr. ;

Mirnics, Karoly ;

Futai, Kensuke ;

Akbarian, Schahram .

JOURNAL OF NEUROSCIENCE, 2013, 33 (29) :11839-+

[6] Breaking the Code of DNA Binding Specificity of TAL-Type III Effectors [J].

Boch, Jens ;

Scholze, Heidi ;

Schornack, Sebastian ;

Landgraf, Angelika ;

Hahn, Simone ;

Kay, Sabine ;

Lahaye, Thomas ;

Nickstadt, Anja ;

Bonas, Ulla .

SCIENCE, 2009, 326 (5959) :1509-1512

[7] Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex [J].

Cheung, Iris ;

Shulha, Hennady P. ;

Jiang, Yan ;

Matevossian, Anouch ;

Wang, Jie ;

Weng, Zhiping ;

Akbarian, Schahram .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (19) :8824-8829

[8] Nuclear Aggregation of Olfactory Receptor Genes Governs Their Monogenic Expression [J].

Clowney, E. Josephine ;

LeGros, Mark A. ;

Mosley, Colleen P. ;

Clowney, Fiona G. ;

Markenskoff-Papadimitriou, Eirene C. ;

Myllys, Markko ;

Barnea, Gilad ;

Larabell, Carolyn A. ;

Lomvardas, Stavros .

CELL, 2012, 151 (04) :724-737

[9] Binding of TFIIIC to SINE Elements Controls the Relocation of Activity-Dependent Neuronal Genes to Transcription Factories [J].

Crepaldi, Luca ;

Policarpi, Cristina ;

Coatti, Alessandro ;

Sherlock, William T. ;

Jongbloets, Bart C. ;

Down, Thomas A. ;

Riccio, Antonella .

PLOS GENETICS, 2013, 9 (08)

[10]

Crocker J, 2013, NAT METHODS, V10, P762, DOI [10.1038/NMETH.2543, 10.1038/nmeth.2543]

← 1 2 3 4 5 6 7 8 →