The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
A CTCF-independent role for cohesin in tissue-specific transcription
Open accessAbstract
The cohesin protein complex holds sister chromatids in dividing cells together and is essential for chromosome segregation. Recently, cohesin has been implicated in mediating transcriptional insulation, via its interactions with CTCF. Here, we show in different cell types that cohesin functionally behaves as a tissue-specific transcriptional regulator, independent of CTCF binding. By performing matched genome-wide binding assays (ChIP-seq) in human breast cancer cells (MCF-7), we discovered thousands of genomic sites that share cohesin and estrogen receptor alpha (ER) yet lack CTCF binding. By use of human hepatocellular carcinoma cells (HepG2), we found that liver-specific transcription factors colocalize with cohesin independently of CTCF at liver-specific targets that are distinct from those found in breast cancer cells. Furthermore, estrogen-regulated genes are preferentially bound by both ER and cohesin, and functionally, the silencing of cohesin caused aberrant re-entry of breast cancer cells into cell cycle after hormone treatment. We combined chromosomal interaction data in MCF-7 cells with our cohesin binding data to show that cohesin is highly enriched at ER-bound regions that capture inter-chromosomal loop anchors. Together, our data show that cohesin cobinds across the genome with transcription factors independently of CTCF, plays a functional role in estrogen-regulated transcription, and may help to mediate tissue-specific transcriptional responses via long-range chromosomal interactions.
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Citations
Cites
Histone modifications at human enhancers reflect global cell-type-specific gene expression
Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533
Robertson, G., Hirst, M., Bainbridge, M., Bilenky, M., Zhao, Y., Zeng, T., Euskirchen, G., Bernier, B., Varhol, R., Delaney, A., et al. (2007) · Nature Methods · doi:10.1038/nmeth1068 · Cited by 1,454
Cohesin mediates transcriptional insulation by CCCTC-binding factor
Wendt, K. S., Yoshida, K., Itoh, T., Bando, M., Koch, B., Schirghuber, E., Tsutsumi, S., Nagae, G., Ishihara, K., Mishiro, T., et al. (2008) · Nature · doi:10.1038/nature06634 · Cited by 1,193
Krantz, I. D., McCallum, J., DeScipio, C., Kaur, M., Gillis, L. A., Yaeger, D., Jukofsky, L., Wasserman, N., Bottani, A., Morris, C. A., et al. (2004) · Nature Genetics · doi:10.1038/ng1364 · Cited by 713
Cuddapah, S., Jothi, R., Schones, D. E., Roh, T.-Y., Cui, K., & Zhao, K. (2009) · Genome Research · doi:10.1101/gr.082800.108 · Cited by 637 · cited 2×
“independent of cell type (Cuddapah et al. 2008; Heintzman et al. 2009), we were not surprised to find that the majority of CTCF”
BackgroundCTCF physically links cohesin to chromatin
Rubio, E. D., Reiss, D. J., Welcsh, P. L., Disteche, C. M., Filippova, G. N., Baliga, N. S., Aebersold, R., Ranish, J. A., & Krumm, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801273105 · Cited by 511
Cited by
An atlas of active enhancers across human cell types and tissues
The FANTOM Consortium, Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., et al. (2014) · Nature · doi:10.1038/nature12787 · Cited by 2,550
Mediator and cohesin connect gene expression and chromatin architecture
Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., et al. (2010) · Nature · doi:10.1038/nature09380 · Cited by 1,939
Transcriptional enhancers: from properties to genome-wide predictions
Shlyueva, D., Stampfel, G., & Stark, A. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3682 · Cited by 1,356
Long-range enhancer–promoter contacts in gene expression control
Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102
Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation
Li, W., Notani, D., Ma, Q., Tanasa, B., Nunez, E., Chen, A. Y., Merkurjev, D., Zhang, J., Ohgi, K., Song, X., et al. (2013) · Nature · doi:10.1038/nature12210 · Cited by 1,049
Metadata
- Authors
- Schmidt, D., Schwalie, P. C., Ross-Innes, C. S., Hurtado, A., Brown, G. D., Carroll, J. S., Flicek, P., & Odom, D. T.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-03-10
- Volume
- 20
- Issue
- 5
- Pages
- 578-588
- ISSN
- 1088-9051 (ISSN-L)
- OpenAlex
- W2154968323
- Cited by
- 358
- References
- 6
- Type
- posted content
- Language
- en
- Open access
- hybrid
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- Schmidt, D., Schwalie, P. C., Ross-Innes, C. S., Hurtado, A., Brown, G. D., Carroll, J. S., Flicek, P., & Odom, D. T. (2010). A CTCF-independent role for cohesin in tissue-specific transcription. Genome Research. https://doi.org/10.1101/gr.100479.109
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