Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

HDAC1 and HDAC2 collectively regulate intestinal stem cell homeostasis.

Author information

Affiliations

  • 1. *Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands; Tygat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; and Cancer Genomics Center, Utrecht, The Netherlands.
      Authors
    • Zimberlin CD 1
    • Lancini C 1
    • Sno R 1
    • Rosekrans SL 1
    • McLean CM 1
    • Vlaming H 1
    • van den Brink GR 1
    • Bots M 1
    • Medema JP 1
    (9 authors)
  • 2. *Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands; Tygat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; and Cancer Genomics Center, Utrecht, The Netherlands
      Authors
    • Dannenberg JH 2
    (1 author)

ORCIDs linked to this article

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 03 Feb 2015, 29(5):2070-2080
https://doi.org/10.1096/fj.14-257931 PMID: 25648995 

Abstract 

Histone deacetylases (HDACs) are posttranslational modifiers that deacetylate proteins. Despite their crucial role in numerous biological processes, the use of broad-range HDAC inhibitors (HDACi), has shown clinical efficacy. However, undesired side effects highlight the necessity to better understand the biology of different HDACs and target the relevant HDACs. Using a novel mouse model, in which HDAC1 and HDAC2 can be simultaneously deleted in the intestine of adult mice, we show that the simultaneous deletion of HDAC1 and HDAC2 leads to a rapid loss of intestinal homeostasis. Importantly, this deletion cannot be sustained, and 8 days after initial ablation, stem cells that have escaped HDAC1 or HDAC2 deletion swiftly repopulate the intestinal lining. In vitro ablation of HDAC1 and HDAC2 using intestinal organoid cultures resulted in a down-regulation of multiple intestinal stem cell markers and functional loss of clonogenic capacity. Importantly, treatment of wild-type organoids with class I-specific HDACi MS-275 also induced a similar loss of stemness, providing a possible rationale for the gastrointestinal side effects often observed in HDACi-treated patients. In conclusion, these data show that HDAC1 and HDAC2 have a redundant function and are essential to maintain intestinal homeostasis.

Full text links 

Read article at publisher's site: https://doi.org/10.1096/fj.14-257931

References 

Articles referenced by this article (34)

Show 10 more references (10 of 34)

Citations & impact 

Impact metrics

30
Citations
Jump to Citations
9
Data citations
Jump to Data

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/3385650
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/3385650

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1096/fj.14-257931

Supporting
Mentioning
Contrasting
4
33
0

Article citations

Go to all (30) article citations

Data 

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Funding 

Funders who supported this work.

KWF Kankerbestrijding (4)