Methylated cis-regulatory elements mediate KLF4-denpendent gene transactivation and cell migration
- Indiana University School of Medicine, United States
- Johns Hopkins University School of Medicine, United States
Abstract
Altered DNA methylation status is associated with human diseases and cancer; however, the underlying molecular mechanisms remain elusive. We previously identified many human transcription factors, including Krüppel-like factor 4 (KLF4), as sequence-specific DNA methylation readers that preferentially recognize methylated CpG (mCpG), here we report the biological function of mCpG-dependent gene regulation by KLF4 in glioblastoma cells. We show that KLF4 promotes cell adhesion, migration, and morphological changes, all of which are abolished by R458A mutation. Surprisingly, 116 genes are directly activated via mCpG-dependent KLF4 binding activity. In-depth mechanistic studies reveal that recruitment of KLF4 to the methylated cis-regulatory elements of these genes result in chromatin remodeling and transcription activation. Our study demonstrates a new paradigm of DNA methylation-mediated gene activation and chromatin remodeling, and provides a general framework to dissect the biological functions of DNA methylation readers and effectors.
Data availability
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Methylation DNA mediated KLF4 binding activity in glioblastoma cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE97632).
Article and author information
Author details
Funding
National Institutes of Health (R01NS091165)
- Shuli Xia
National Institutes of Health (EY024580)
- Jiang Qian
National Institutes of Health (R01 GM111514)
- Heng Zhu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bing Ren, University of California, San Diego School of Medicine, United States
Version history
- Received: August 20, 2016
- Accepted: May 24, 2017
- Accepted Manuscript published: May 29, 2017 (version 1)
- Version of Record published: June 9, 2017 (version 2)
Copyright
© 2017, Wan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Methylated cis-regulatory elements mediate KLF4-denpendent gene transactivation and cell migration
eLife 6:e20068.
https://doi.org/10.7554/eLife.20068
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