The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
BRD4 Coordinates Recruitment of Pause Release Factor P-TEFb and the Pausing Complex NELF/DSIF To Regulate Transcription Elongation of Interferon-Stimulated Genes
Open accessAbstract
RNA polymerase II (Pol II) and the pausing complex, NELF and DSIF, are detected near the transcription start site (TSS) of many active and silent genes. Active transcription starts when the pause release factor P-TEFb is recruited to initiate productive elongation. However, the mechanism of P-TEFb recruitment and regulation of NELF/DSIF during transcription is not fully understood. We investigated this question in interferon (IFN)-stimulated transcription, focusing on BRD4, a BET family protein that interacts with P-TEFb. Besides P-TEFb, BRD4 binds to acetylated histones through the bromodomain. We found that BRD4 and P-TEFb, although not present prior to IFN treatment, were robustly recruited to IFN-stimulated genes (ISGs) after stimulation. Likewise, NELF and DSIF prior to stimulation were hardly detectable on ISGs, which were strongly recruited after IFN treatment. A shRNA-based knockdown assay of NELF revealed that it negatively regulates the passage of Pol II and DSIF across the ISGs during elongation, reducing total ISG transcript output. Analyses with a BRD4 small-molecule inhibitor showed that IFN-induced recruitment of P-TEFb and NELF/DSIF was under the control of BRD4. We suggest a model where BRD4 coordinates both positive and negative regulation of ISG elongation.
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Cites
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080 · cited 2×
“Given that a wide range of genes are stimulated by JAK/STAT pathways in addition to ISGs, regulating cell growth, development, and responses to various external signals, it is reasonable to assume that the pattern of NELF/DSIF occupancy revealed in this study may represent a fairly common feature (30, 31, 33, 51).”
BackgroundSelective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Self-citationSuppression of inflammation by a synthetic histone mimic
Nicodeme, E., Jeffrey, K. L., Schaefer, U., Beinke, S., Dewell, S., Chung, C.-W., Chandwani, R., Marazzi, I., Wilson, P., Coste, H., et al. (2010) · Nature · doi:10.1038/nature09589 · Cited by 1,563
Wada, T., Takagi, T., Yamaguchi, Y., Ferdous, A., Imai, T., Hirose, S., Sugimoto, S., Yano, K., Hartzog, G. A., Winston, F., et al. (1998) · Genes & Development · doi:10.1101/gad.12.3.343 · Cited by 750
Cited by
BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure
Anand, P., Brown, J. D., Lin, C. Y., Qi, J., Zhang, R., Artero, P. C., Alaiti, M. A., Bullard, J., Alazem, K., Margulies, K. B., et al. (2013) · Cell · doi:10.1016/j.cell.2013.07.013 · Cited by 406
“Previous studies in NIH 3T3 cells and macrophages have demonstrated that BRD4 interacts with P-TEFb and facilitates stimulus-coupled recruitment of P-TEFb to target promoters (Hargreaves et al., 2009; Patel et al., 2013).”
Taniguchi, Y. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17111849 · Cited by 336
Regulation of type I interferon signaling in immunity and inflammation: A comprehensive review
Chen, K., Liu, J., & Cao, X. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.03.008 · Cited by 312
H2A.Z: a molecular rheostat for transcriptional control
Subramanian, V., Fields, P. A., & Boyer, L. A. (2015) · F1000Prime Reports · doi:10.12703/p7-01 · Cited by 102
DeMars, K. M., Yang, C., Castro-Rivera, C. I., & Candelario-Jalil, E. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.02.096 · Cited by 66
Metadata
- Authors
- Patel, M. C., Debrosse, M., Smith, M., Dey, A., Huynh, W., Sarai, N., Heightman, T. D., Tamura, T., & Ozato, K.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2013-06
- Volume
- 33
- Issue
- 12
- Pages
- 2497-2507
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2001799880
- Cited by
- 183
- References
- 4
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- green
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- Patel, M. C., Debrosse, M., Smith, M., Dey, A., Huynh, W., Sarai, N., Heightman, T. D., Tamura, T., & Ozato, K. (2013). BRD4 Coordinates Recruitment of Pause Release Factor P-TEFb and the Pausing Complex NELF/DSIF To Regulate Transcription Elongation of Interferon-Stimulated Genes. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.01180-12
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