Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection

被引：353

作者：

Flavell, Steven W. ^{[1
,2
,3
,4
]}

Kim, Tae-Kyung ^{[1
,2
,3
]}

Gray, Jesse M. ^{[1
,2
,3
]}

Harmin, David A. ^{[1
,2
,3
,5
]}

Hemberg, Martin ^{[6
]}

Hong, Elizabeth J. ^{[1
,2
,3
,4
]}

Markenscoff-Papadimitriou, Eirene ^{[1
,2
,3
]}

Bear, Daniel M. ^{[1
,2
,3
]}

Greenberg, Michael E. ^{[1
,2
,3
]}

机构：

[1] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA

[5] Childrens Hosp, Informat Program, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA

[6] Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA

来源：

NEURON | 2008年 / 60卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.neuron.2008.11.029

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Although many transcription factors are known to control important aspects of neural development, the genome-wide programs that are directly regulated by these factors are not known. We have characterized the genetic program that is activated by MEF2, a key regulator of activity-dependent synapse development. These MEF2 target genes have diverse functions at synapses, revealing a broad role for MEF2 in synapse development. Several of the MEF2 targets are mutated in human neurological disorders including epilepsy and autism spectrum disorders, suggesting that these disorders may be caused by disruption of an activity-dependent gene program that controls synapse development. Our analyses also reveal that neuronal activity promotes alternative polyadenylation site usage at many of the MEF2 target genes, leading to the production of truncated mRNAs that may have different functions than their full-length counterparts. Taken together, these analyses suggest that the ubiquitously expressed transcription factor MEF2 regulates an intricate transcriptional program in neurons that controls synapse development.

引用

页码：1022 / 1038

页数：17

共 52 条

[1] Dendrite development regulated by CREST, a calcium-regulated transcriptional activator [J].

Aizawa, H ;

Hu, SC ;

Bobb, K ;

Balakrishnan, K ;

Ince, G ;

Gurevich, I ;

Cowan, M ;

Ghosh, A .

SCIENCE, 2004, 303 (5655) :197-202

[2] MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function [J].

Barbosa, Ana C. ;

Kim, Mi-Sung ;

Ertunc, Mert ;

Adachi, Megumi ;

Nelson, Erika D. ;

McAnally, John ;

Richardson, James A. ;

Kavalali, Ege T. ;

Monteggia, Lisa M. ;

Bassel-Duby, Rhonda ;

Olson, Eric N. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (27) :9391-9396

[3] Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture [J].

Barco, A ;

Alarcon, JM ;

Kandel, ER .

CELL, 2002, 108 (05) :689-703

[4]

Boehm S, 1997, J NEUROSCI, V17, P4066

[5] Developmental remodeling of the retinogeniculate synapse [J].

Chen, CF ;

Regehr, WG .

NEURON, 2000, 28 (03) :955-966

[6] Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking [J].

Chowdhury, Shoaib ;

Shepherd, Jason D. ;

Okuno, Hiroyuki ;

Lyford, Gregory ;

Petralia, Ronald S. ;

Plath, Niels ;

Kuhl, Dietmar ;

Huganir, Richard L. ;

Worley, Paul F. .

NEURON, 2006, 52 (03) :445-459

[7] X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment [J].

Dibbens, Leanne M. ;

Tarpey, Patrick S. ;

Hynes, Kim ;

Bayly, Marta A. ;

Scheffer, Ingrid E. ;

Smith, Raffaella ;

Bomar, Jamee ;

Sutton, Edwina ;

Vandeleur, Lucianne ;

Shoubridge, Cheryl ;

Edkins, Sarah ;

Turner, Samantha J. ;

Stevens, Claire ;

O'Meara, Sarah ;

Tofts, Calli ;

Barthorpe, Syd ;

Buck, Gemma ;

Cole, Jennifer ;

Halliday, Kelly ;

Jones, David ;

Lee, Rebecca ;

Madison, Mark ;

Mironenko, Tatiana ;

Varian, Jennifer ;

West, Sofie ;

Widaa, Sara ;

Wray, Paul ;

Teague, John ;

Dicks, Ed ;

Butler, Adam ;

Menzies, Andrew ;

Jenkinson, Andrew ;

Shepherd, Rebecca ;

Gusella, James F. ;

Afawi, Zaid ;

Mazarib, Aziz ;

Neufeld, Miriam Y. ;

Kivity, Sara ;

Lev, Dorit ;

Lerman-Sagie, Tally ;

Korczyn, Amos D. ;

Derry, Christopher P. ;

Sutherland, Grant R. ;

Friend, Kathryn ;

Shaw, Marie ;

Corbett, Mark ;

Kim, Hyung-Goo ;

Geschwind, Daniel H. ;

Thomas, Paul ;

Haan, Eric .

NATURE GENETICS, 2008, 40 (06) :776-781

[8] A role in learning for SRF:: Deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context [J].

Etkin, A ;

Alarcón, JM ;

Weisberg, SP ;

Touzani, K ;

Huang, YY ;

Nordheim, A ;

Kandel, ER .

NEURON, 2006, 50 (01) :127-143

[9] Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system [J].

Flavell, Steven W. ;

Greenberg, Michael E. .

ANNUAL REVIEW OF NEUROSCIENCE, 2008, 31 :563-590

[10] Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number [J].

Flavell, SW ;

Cowan, CW ;

Kim, TK ;

Greer, PL ;

Lin, YX ;

Paradis, S ;

Griffith, EC ;

Hu, LS ;

Chen, CF ;

Greenberg, ME .

SCIENCE, 2006, 311 (5763) :1008-1012

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