APA
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Bharadwaj, R. A., Peter, C., Jiang, Y., Roussos, P., Vogel-Ciernia, A., Shen, E. Y., … Akbarian, S. (2014). CONSERVED HIGHER ORDER CHROMATIN REGULATES NMDA RECEPTOR GENE EXPRESSION AND COGNITION. Neuron.
Chicago/Turabian
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Bharadwaj, Rahul A., C. Peter, Yan Jiang, P. Roussos, Annie Vogel-Ciernia, Erica Y. Shen, A. Mitchell, et al. “CONSERVED HIGHER ORDER CHROMATIN REGULATES NMDA RECEPTOR GENE EXPRESSION AND COGNITION.” Neuron (2014).
MLA
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Bharadwaj, Rahul A., et al. “CONSERVED HIGHER ORDER CHROMATIN REGULATES NMDA RECEPTOR GENE EXPRESSION AND COGNITION.” Neuron, 2014.
BibTeX Click to copy
@article{rahul2014a,
title = {CONSERVED HIGHER ORDER CHROMATIN REGULATES NMDA RECEPTOR GENE EXPRESSION AND COGNITION},
year = {2014},
journal = {Neuron},
author = {Bharadwaj, Rahul A. and Peter, C. and Jiang, Yan and Roussos, P. and Vogel-Ciernia, Annie and Shen, Erica Y. and Mitchell, A. and Mao, Wenjie and Whittle, Catheryne and Dincer, Aslihan and Jakovcevski, Mira and Pothula, V. and Rasmussen, T. and Giakoumaki, S. and Bitsios, P. and Sherif, A. and Gardner, P. and Ernst, P. and Ghose, S. and Sklar, P. and Haroutunian, V. and Tamminga, C. and Myers, R. and Futai, K. and Wood, M. and Akbarian, S.}
}
3-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 megabase 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-methyltransferase 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.