Chromatin modifications that support acetylcholine receptor gene activation are established during muscle cell determination and differentiation.
Chromatin modifications that support acetylcholine receptor gene activation are established during muscle cell determination and differentiation.
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DOI：
10.1007/s11033-010-0227-7
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发表时间：
2011-02
影响因子：
2.8
通讯作者：
Fromm L
中科院分区：
文献类型：
--
作者：
Herndon CA;Snell J;Fromm L
乙酰胆碱受体（achr）在肌肉突触后区域的定位部分是由转录机制介导的。调控转录的一个重要途径是将染色质上的组蛋白修饰靶向到不同的基因位点。利用染色质免疫沉淀法，我们研究了AChR epsilon亚基位点上某些组蛋白修饰的发育调控，包括赖氨酸残基K4和K27的甲基化以及K9和K14的乙酰化。我们在细胞培养中模拟了肌肉发育的各个阶段，包括预先确定的细胞、固定但未分化的成肌细胞和分化的肌管，并通过神经调节蛋白（NRG） 1刺激肌管来模拟突触肌管核。我们发现，在NRG1刺激之前，与转录激活相关的组蛋白修饰模式针对肌管中的AChR epsilon亚基位点，并且在NRG1加入后不会发生变化。相反，我们发现在肌肉细胞的确定和分化过程中，特定的组蛋白修饰是针对AChR epsilon亚基位点的。在该基因中，在K4，二甲基化在肌肉细胞的确定过程中被诱导，而三甲基化在分化过程中被诱导。在K27位点，三甲基化的缺失和单甲基化的出现发生在决定和分化过程中。此外，在该基因的上游区域，K4二甲基化和三甲基化以及K9/14乙酰化以不同的发育模式被诱导，这可能反映了一个功能调控元件。这些结果表明突触信号并不直接针对组蛋白修饰，而是转录激活所需的组蛋白修饰模式先前在肌肉发育过程中的一系列步骤中建立。
Localization of acetylcholine receptors (AChRs) to the postsynaptic region of muscle is mediated in part by transcriptional mechanisms. An important way of regulating transcription is through targeting histone modifications on chromatin to distinct gene loci. Using chromatin immunoprecipitation, we examined the developmental regulation of certain histone modifications at the AChR epsilon subunit locus, including methylations at lysine residues K4 and K27 and acetylations at K9 and K14. We modeled various stages of muscle development in cell culture, including pre-determined cells, committed but undifferentiated myoblasts, and differentiated myotubes, and modeled synaptic myotube nuclei by stimulating myotubes with neuregulin (NRG) 1. We found that a pattern of histone modifications associated with transcriptional activation is targeted to the AChR epsilon subunit locus in myotubes prior to stimulation with NRG1 and does not change upon addition of NRG1. Instead, we found that during muscle cell determination and differentiation, specific histone modifications are targeted to the AChR epsilon subunit locus. Within the gene, at K4, dimethylation is induced during muscle cell determination, while trimethylation is induced during differentiation. At K27, loss of trimethylation and appearance of monomethylation occurs during determination and differentiation. In addition, in a region upstream of the gene, K4 di- and trimethylation, and K9/14 acetylation are induced in a distinct developmental pattern, which may reflect a functional regulatory element. These results suggest synaptic signaling does not directly target histone modifications but rather the histone modification pattern necessary for transcriptional activation is previously established in a series of steps during muscle development.
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影响因子：
64.8
作者：
Santos-Rosa, H;Schneider, R;Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
16.2
作者：
CHU, GC;MOSCOSO, LM;MERLIE, JP
通讯作者：
MERLIE, JP
影响因子：
64.5
作者：
DeChiara, TM;Bowen, DC;Yancopoulos, GD
通讯作者：
Yancopoulos, GD
影响因子：
21.3
作者：
Schneider, R;Bannister, AJ;Kouzarides, T
通讯作者：
Kouzarides, T
DOI：
10.1111/j.1432-1033.1994.00353.x
发表时间：
1994-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
DURR, I;NUMBERGER, M;WITZEMANN, V
通讯作者：
WITZEMANN, V