2026-07-24T06:28:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/68212024-11-29T14:34:48Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Garcia-Carpizo, Veronica
author
Ruiz-Llorente, Sergio
author
Sarmentero, Jacinto
author
Graña Castro, Osvaldo
author
Pisano, David G
author
Barrero, Maria Jose
funder
Fundación Lilly
2018-12-12T12:02:52Z
2018-12-12T12:02:52Z
2018
Epigenetics Chromatin. 2018;11(1):30.
10.1186/s13072-018-0197-x
1756-8935
1756-8935
Epigenetics & chromatin
29884215
http://hdl.handle.net/20.500.12105/6821
BACKGROUND: The reported antitumor activity of the BET family bromodomain inhibitors has prompted the development of inhibitors against other bromodomains. However, the human genome encodes more than 60 different bromodomains and most of them remain unexplored. RESULTS: We report that the bromodomains of the histone acetyltransferases CREBBP/EP300 are critical to sustain the proliferation of human leukemia and lymphoma cell lines. EP300 is very abundant at super-enhancers in K562 and is coincident with sites of GATA1 and MYC occupancy. In accordance, CREBBP/EP300 bromodomain inhibitors interfere with GATA1- and MYC-driven transcription, causing the accumulation of cells in the G0/G1 phase of the cell cycle. The CREBBP/CBP30 bromodomain inhibitor CBP30 displaces CREBBP and EP300 from GATA1 and MYC binding sites at enhancers, resulting in a decrease in the levels of histone acetylation at these regulatory regions and consequently reduced gene expression of critical genes controlled by these transcription factors. CONCLUSIONS: Our data shows that inhibition of CREBBP/EP300 bromodomains can interfere with oncogene-driven transcriptional programs in cancer cells and consequently hold therapeutic potential.
eng
Bromodomains
Cancer
Epigenetics
Proliferation
CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation
journal article
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URL
https://repisalud.isciii.es/bitstreams/744d521c-808a-4a65-ae4f-e2e78ccc03d7/download
File
MD5
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application/pdf
CREBBPEP300bromodomains _ 2018.pdf
URL
https://repisalud.isciii.es/bitstreams/77d2c712-6223-4b58-8639-f5b5a9e12e97/download
File
MD5
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text/plain
CREBBPEP300bromodomains _ 2018.pdf.txt