Genome-wide identification and characterization of functional neuronal activity-dependent enhancers.
Genome-wide identification and characterization of functional neuronal activity-dependent enhancers.
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DOI：
10.1038/nn.3808
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发表时间：
2014-10
影响因子：
25
通讯作者：
Greenberg, Michael E.
中科院分区：
文献类型：
--
作者：
Malik, Athar N.;Vierbuchen, Thomas;Hemberg, Martin;Rubin, Alex A.;Ling, Emi;Couch, Cameron H.;Stroud, Hume;Spiegel, Ivo;Farh, Kyle Kai-How;Harmin, David A.;Greenberg, Michael E.
依赖经验的基因转录是神经系统发育和功能所必需的。然而，控制这一基因表达程序的DNA调控元件并没有得到很好的定义。在这里，我们描述了在整个基因组中发挥作用的增强子，这些增强子在小鼠皮质神经元中介导活性依赖的转录。我们发现，组蛋白H3赖氨酸4(H3K4me1)的单甲基化和转录共激活因子CREBBP(CBP)的结合增强了组蛋白H3赖氨酸27(H3K27ac)在皮质神经元膜去极化上的乙酰化作用，从而调节活性依赖的转录。这些增强子的一个子集似乎需要FOS的结合，而以前人们认为FOS主要与启动子结合。这些发现表明，FOS在增强子中起着控制活性依赖的基因程序的作用，这些基因程序对神经系统功能至关重要，并提供了功能上的顺式调节元件资源，这些顺式调节元件可能有助于洞察有助于大脑发育和疾病的遗传变异。
Experience-dependent gene transcription is required for nervous system development and function. However, the DNA regulatory elements that control this program of gene expression are not well defined. Here we characterize the enhancers that function across the genome to mediate activity-dependent transcription in mouse cortical neurons. We find that the subset of enhancers enriched for monomethylation of histone H3 lysine 4 (H3K4me1) and binding of the transcriptional co-activator CREBBP (CBP) that shows increased acetylation of histone H3 lysine 27 (H3K27ac) upon membrane depolarization of cortical neurons functions to regulate activity-dependent transcription. A subset of these enhancers appears to require binding of FOS, which previously was thought to bind primarily to promoters. These findings suggest that FOS functions at enhancers to control activity-dependent gene programs that are critical for nervous system function and provide a resource of functional cis-regulatory elements that may give insight into the genetic variants that contribute to brain development and disease.
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影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
64.8
作者：
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
25
作者：
Chang, Michael C.;Park, Joo Min;Pelkey, Kenneth A.;Grabenstatter, Heidi L.;Xu, Desheng;Linden, David J.;Sutula, Thomas P.;McBain, Chris J.;Worley, Paul F.
通讯作者：
Worley, Paul F.
影响因子：
4.4
作者：
HSU, YC;PERIN, MS
通讯作者：
PERIN, MS
DOI：
10.1126/science.1222794
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maurano MT;Humbert R;Rynes E;Thurman RE;Haugen E;Wang H;Reynolds AP;Sandstrom R;Qu H;Brody J;Shafer A;Neri F;Lee K;Kutyavin T;Stehling-Sun S;Johnson AK;Canfield TK;Giste E;Diegel M;Bates D;Hansen RS;Neph S;Sabo PJ;Heimfeld S;Raubitschek A;Ziegler S;Cotsapas C;Sotoodehnia N;Glass I;Sunyaev SR;Kaul R;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA