Gcn4 Binding in Coding Regions Can Activate Internal and Canonical 5' Promoters in Yeast.
Gcn4 Binding in Coding Regions Can Activate Internal and Canonical 5' Promoters in Yeast.
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DOI：
10.1016/j.molcel.2018.03.007
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发表时间：
2018-04-19
期刊：
影响因子：
16
通讯作者：
Hinnebusch AG
中科院分区：
文献类型：
--
作者：
Rawal Y;Chereji RV;Valabhoju V;Qiu H;Ocampo J;Clark DJ;Hinnebusch AG
gcn 4是一种由氨基酸饥饿诱导的酵母转录激活因子。ChIP-seq分析揭示了饥饿细胞中Gcn 4占据的546个基因组位点，占Gcn 4结合基序的约30%。令人惊讶的是，只有~40%的结合位点在启动子中，其中只有~60%激活转录，表明对Gcn 4功能的广泛负控制。其余约300个Gcn 4结合位点中的大多数在编码序列（CDS）内，其中约75个代表Gcn 4诱导基因附近的唯一结合位点。许多这样的非常规网站之间的映射不同的反义和亚基因有义转录诱导CDS内，邻近诱导TBP峰值一致的隐蔽，双向内部启动子的GCN 4激活。突变分析证实，Gcn 4的CDS内的网站可以激活亚基因和全长转录相同或相邻的基因，显示功能Gcn 4结合不限于启动子。我们的研究结果表明，内部启动子可以调节的激活剂，在传统的5′-定位启动子的功能。Rawal等人发现，酵母转录因子Gcn 4经常结合在酵母细胞中核小体占据的蛋白质编码区内，并且这些事件的相当大一部分赋予隐藏的内部启动子以及相同或相邻基因处的典型5′-定位启动子的激活。
Gcn4 is a yeast transcriptional activator induced by amino acid starvation. ChIP-seq analysis revealed 546 genomic sites occupied by Gcn4 in starved cells, representing ~30% of Gcn4 binding-motifs. Surprisingly, only ~40% of the bound sites are in promoters, of which only ~60% activate transcription, indicating extensive negative control over Gcn4 function. Most of the remaining ~300 Gcn4-bound sites are within coding sequences (CDS), with ~75 representing the only bound sites near Gcn4-induced genes. Many such unconventional sites map between divergent antisense and sub-genic sense transcripts induced within CDS, adjacent to induced TBP peaks—consistent with Gcn4 activation of cryptic, bidirectional internal promoters. Mutational analysis confirms that Gcn4 sites within CDS can activate sub-genic and full-length transcripts from the same or adjacent genes, showing that functional Gcn4 binding is not confined to promoters. Our results show that internal promoters can be regulated by an activator that functions at conventional 5′-positioned promoters. Rawal et al. showed that yeast transcription factor Gcn4 frequently binds within nucleosome-occupied protein coding regions in yeast cells, and that a substantial fraction of these events confer activation of cryptic internal promoters as well as canonical 5′-positioned promoters at the same or adjacent genes.
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影响因子：
3.5
作者：
Good, Paul D.;Kendall, Ann;Engelke, David R.
通讯作者：
Engelke, David R.
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
14.9
作者：
Bailey TL;Johnson J;Grant CE;Noble WS
通讯作者：
Noble WS
影响因子：
48
作者：
Hesselberth, Jay R.;Chen, Xiaoyu;Zhang, Zhihong;Sabo, Peter J.;Sandstrom, Richard;Reynolds, Alex P.;Thurman, Robert E.;Neph, Shane;Kuehn, Michael S.;Noble, William S.;Fields, Stanley;Stamatoyannopoulos, John A.
通讯作者：
Stamatoyannopoulos, John A.
DOI：
10.1073/pnas.81.24.7860
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GUARENTE, L;HOAR, E
通讯作者：
HOAR, E