1. Chromosomes and Gene Expression
  2. Immunology and Inflammation

Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility

  1. Chan-Wang Jerry Lio  Is a corresponding author
  2. Jiayuan Zhang
  3. Edahí González-Avalos
  4. Patrick G Hogan
  5. Xing Chang  Is a corresponding author
  6. Anjana Rao  Is a corresponding author
  1. La Jolla Institute For Allergy & Immunology, United States
  2. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, China
  3. La Jolla Institute For Allergy and Immunology, United States
https://doi.org/10.7554/eLife.18290
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  1. Chan-Wang Jerry Lio
  2. Jiayuan Zhang
  3. Edahí González-Avalos
  4. Patrick G Hogan
  5. Xing Chang
  6. Anjana Rao
(2016)
Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility
eLife 5:e18290.
https://doi.org/10.7554/eLife.18290
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  3. Download .RIS

Abstract

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igκ enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igκ enhancer function by modulating the modification status of DNA.

Data availability

The following data sets were generated
    1. Chang X
    2. Lio CW
    3. Zhang J
    4. Hogan PG and Rao A
    (2016) Role of Tet proteins in B cell development
    Publicly available at the NCBI BioProject database (accession no: PRJNA324297).
    http://www.ncbi.nlm.nih.gov/bioproject/PRJNA324297
The following previously published data sets were used

Article and author information

Author details

  1. Chan-Wang Jerry Lio

    Division of Signaling and Gene Expression, La Jolla Institute For Allergy & Immunology, San Diego, United States
    For correspondence
    lio@lji.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3876-6741

  2. Jiayuan Zhang

    Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Edahí González-Avalos

    Division of Signaling and Gene Expression, La Jolla Institute For Allergy and Immunology, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Patrick G Hogan

    Division of Signaling and Gene Expression, La Jolla Institute For Allergy and Immunology, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Xing Chang

    Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
    For correspondence
    changxing@sibs.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

  6. Anjana Rao

    Division of Signaling and Gene Expression, La Jolla Institute For Allergy and Immunology, San Diego, United States
    For correspondence
    arao@lji.org
    Competing interests
    The authors declare that no competing interests exist.

Funding

Cancer Research Institute (Irvington Postdoctoral Fellowship)

  • Chan-Wang Jerry Lio

National Institutes of Health (AI44432)

  • Anjana Rao

National Institutes of Health (CA151535)

  • Anjana Rao

Leukemia and Lymphoma Society (6187-12)

  • Anjana Rao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christopher K Glass, University of California, San Diego, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal works were performed according to protocol (AP128-AR2-0516) approved by the Institutional Animal Care and Use Committee at La Jolla Institute.

Version history

  1. Received: May 28, 2016
  2. Accepted: November 18, 2016
  3. Accepted Manuscript published: November 21, 2016 (version 1)
  4. Version of Record published: December 7, 2016 (version 2)
  5. Version of Record updated: December 8, 2016 (version 3)

Copyright

© 2016, Lio 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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  1. Chan-Wang Jerry Lio
  2. Jiayuan Zhang
  3. Edahí González-Avalos
  4. Patrick G Hogan
  5. Xing Chang
  6. Anjana Rao
(2016)
Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility
eLife 5:e18290.
https://doi.org/10.7554/eLife.18290

Share this article

https://doi.org/10.7554/eLife.18290

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