Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins

Publication Date:
2018-11-08
Publisher:
American Association for the Advancement of Science (AAAS)
Electronic ISSN:
2375-2548
Topics:
Natural Sciences in General
Published by:
http://www.aaas.org/
_version_ 1836399082870931457
autor Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
beschreibung Human FACT (facilitates chromatin transcription) is a multifunctional protein complex that has histone chaperone activity and facilitates nucleosome survival and transcription through chromatin. Anticancer drugs curaxins induce FACT trapping on chromatin of cancer cells (c-trapping), but the mechanism of c-trapping is not fully understood. Here, we show that in cancer cells, FACT is highly enriched within the bodies of actively transcribed genes. Curaxin-dependent c-trapping results in redistribution of FACT from the transcribed chromatin regions to other genomic loci. Using a combination of biochemical and biophysical approaches, we have demonstrated that FACT is bound to and unfolds nucleosomes in the presence of curaxins. This tight binding to the nucleosome results in inhibition of FACT-dependent transcription in vitro in the presence of both curaxins and competitor chromatin, suggesting a mechanism of FACT trapping on bulk nucleosomes (n-trapping).
citation_standardnr 6354939
datenlieferant ipn_articles
feed_id 228416
feed_publisher American Association for the Advancement of Science (AAAS)
feed_publisher_url http://www.aaas.org/
insertion_date 2018-11-08
journaleissn 2375-2548
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Association for the Advancement of Science (AAAS)
quelle Science Advances
relation http://advances.sciencemag.org/cgi/content/short/4/11/eaav2131?rss=1
search_space articles
shingle_author_1 Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
shingle_author_2 Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
shingle_author_3 Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
shingle_author_4 Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
shingle_catch_all_1 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
Human FACT (facilitates chromatin transcription) is a multifunctional protein complex that has histone chaperone activity and facilitates nucleosome survival and transcription through chromatin. Anticancer drugs curaxins induce FACT trapping on chromatin of cancer cells (c-trapping), but the mechanism of c-trapping is not fully understood. Here, we show that in cancer cells, FACT is highly enriched within the bodies of actively transcribed genes. Curaxin-dependent c-trapping results in redistribution of FACT from the transcribed chromatin regions to other genomic loci. Using a combination of biochemical and biophysical approaches, we have demonstrated that FACT is bound to and unfolds nucleosomes in the presence of curaxins. This tight binding to the nucleosome results in inhibition of FACT-dependent transcription in vitro in the presence of both curaxins and competitor chromatin, suggesting a mechanism of FACT trapping on bulk nucleosomes (n-trapping).
Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_catch_all_2 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
Human FACT (facilitates chromatin transcription) is a multifunctional protein complex that has histone chaperone activity and facilitates nucleosome survival and transcription through chromatin. Anticancer drugs curaxins induce FACT trapping on chromatin of cancer cells (c-trapping), but the mechanism of c-trapping is not fully understood. Here, we show that in cancer cells, FACT is highly enriched within the bodies of actively transcribed genes. Curaxin-dependent c-trapping results in redistribution of FACT from the transcribed chromatin regions to other genomic loci. Using a combination of biochemical and biophysical approaches, we have demonstrated that FACT is bound to and unfolds nucleosomes in the presence of curaxins. This tight binding to the nucleosome results in inhibition of FACT-dependent transcription in vitro in the presence of both curaxins and competitor chromatin, suggesting a mechanism of FACT trapping on bulk nucleosomes (n-trapping).
Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_catch_all_3 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
Human FACT (facilitates chromatin transcription) is a multifunctional protein complex that has histone chaperone activity and facilitates nucleosome survival and transcription through chromatin. Anticancer drugs curaxins induce FACT trapping on chromatin of cancer cells (c-trapping), but the mechanism of c-trapping is not fully understood. Here, we show that in cancer cells, FACT is highly enriched within the bodies of actively transcribed genes. Curaxin-dependent c-trapping results in redistribution of FACT from the transcribed chromatin regions to other genomic loci. Using a combination of biochemical and biophysical approaches, we have demonstrated that FACT is bound to and unfolds nucleosomes in the presence of curaxins. This tight binding to the nucleosome results in inhibition of FACT-dependent transcription in vitro in the presence of both curaxins and competitor chromatin, suggesting a mechanism of FACT trapping on bulk nucleosomes (n-trapping).
Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_catch_all_4 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
Human FACT (facilitates chromatin transcription) is a multifunctional protein complex that has histone chaperone activity and facilitates nucleosome survival and transcription through chromatin. Anticancer drugs curaxins induce FACT trapping on chromatin of cancer cells (c-trapping), but the mechanism of c-trapping is not fully understood. Here, we show that in cancer cells, FACT is highly enriched within the bodies of actively transcribed genes. Curaxin-dependent c-trapping results in redistribution of FACT from the transcribed chromatin regions to other genomic loci. Using a combination of biochemical and biophysical approaches, we have demonstrated that FACT is bound to and unfolds nucleosomes in the presence of curaxins. This tight binding to the nucleosome results in inhibition of FACT-dependent transcription in vitro in the presence of both curaxins and competitor chromatin, suggesting a mechanism of FACT trapping on bulk nucleosomes (n-trapping).
Chang, H.-W., Valieva, M. E., Safina, A., Chereji, R. V., Wang, J., Kulaeva, O. I., Morozov, A. V., Kirpichnikov, M. P., Feofanov, A. V., Gurova, K. V., Studitsky, V. M.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_title_1 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
shingle_title_2 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
shingle_title_3 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
shingle_title_4 Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
timestamp 2025-06-30T23:37:19.863Z
titel Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
titel_suche Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins
topic TA-TD
uid ipn_articles_6354939