| Title: |
Transcriptional landscape of the human cell cycle. |
| Authors: |
Yin Liu1,2,3, Sujun Chen1,2,4,5, Su Wang2,3,6, Soares, Fraser4, Fischer, Martin7, Feilong Meng8, Zhou Du2,3,9, Lin, Charles10, Meyer, Clifford3,11, DeCaprio, James A.7, Brown, Myles3,7 myles_brown@dfci.harvard.edu, Liu, X. Shirley3,11 xsliu@jimmy.harvard.edu, Housheng Hansen He4,5 hansenhe@uhnresearch.ca |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America. 3/28/2017, Vol. 114 Issue 13, p3473-3478. 6p. 5 Graphs. |
| Subject Terms: |
*GENE regulatory networks, *HUMAN cell cycle, *CELL cycle, *MAMMALIAN cell cycle, *BREAST cancer |
| Abstract: |
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 histonemodification 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 earlyMphase 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
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