文献详情
Transcriptional landscape of the human cell cycle
文献类型期刊论文
作者Liu, Yin[1];Chen, Sujun[2];Wang, Su[3];Soares, Fraser[4];Fischer, Martin[5];Meng, Feilong[6];Du, Zhou[7];Lin, Charles[8];Meyer, Clifford[9];DeCaprio, James A.[10];Brown, Myles[11];Liu, X. Shirley[12];He, Housheng Hansen[13]
机构
通讯作者Brown, M; Liu, XS (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.; He, HH (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada.; He, HH (reprint author), Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.; Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Brown, M (reprint author), Harvard Med Sch, Boston, MA 02215 USA.; Liu, XS (reprint author), Harvard TH Chan Sch Publ Hlth, Bos
2017
期刊名称PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA影响因子和分区
114
13
页码范围3473-3478
增刊正刊
学科综合性期刊
收录情况SCI(E)(WOS:000397607300073)  
所属部门医院
语言外文
ISSN0027-8424
DOI10.1073/pnas.1617636114
被引频次1
人气指数84
浏览次数84
基金National Natural Science Foundation of China [31329003]; Princess Margaret Cancer Foundation; Canada Foundation for Innovation; Ontario Research Fund [CFI32372]; Natural Sciences and Engineering Research Council of Canada [498706]; NIH [1R01GM099409]; US Public Health Service [R01CA63113, R01CA173023]; German National Academy of Sciences Leopoldina Fellowship; Office of Management, Information, and Research (OMIR) Early Researcher Award; Terry Fox New Investigator Award; Canadian Institutes of Health Research (CIHR) New Investigator Salary Award
关键词GRO-seq; nascent RNA; transcriptional regulation; epigenetics; cell cycle
摘要Steady-state gene expression across the cell cycle has been studied extensively. However, transcriptional gene regulation and the dynamics of histone modification at different cell-cycle stages are largely unknown. By applying a combination of global nuclear run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and histone-modification Chip sequencing (ChIP-seq), we depicted a comprehensive transcriptional landscape at the G0/G1, G1/S, and M phases of breast cancer MCF-7 cells. Importantly, GRO-seq and RNA-seq analysis identified different cell-cycle-regulated genes, suggesting a lag between transcription and steady-state expression during the cell cycle. Interestingly, we identified genes actively transcribed at early M phase that are longer in length and have low expression and are accompanied by a global increase in active histone 3 lysine 4 methylation (H3K4me2) and histone 3 lysine 27 acetylation (H3K27ac) modifications. In addition, we identified 2,440 cell-cycle-regulated enhancer RNAs (eRNAs) that are strongly associated with differential active transcription but not with stable expression levels across the cell cycle. Motif analysis of dynamic eRNAs predicted Kruppel-like factor 4 (KLF4) as a key regulator of G1/S transition, and this identification was validated experimentally. Taken together, our combined analysis characterized the transcriptional and histone-modification profile of the human cell cycle and identified dynamic transcriptional signatures across the cell cycle.
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