Abstract

During eukaryotic evolution, genome size has increased disproportionately to nuclear volume, necessitating greater degrees of chromatin compaction in higher eukaryotes which have evolved several mechanisms for genome compaction. However, it is unknown whether histones themselves have evolved to regulate chromatin compaction. Analysis of histone sequences from 160 eukaryotes revealed that the H2A N-terminus has systematically acquired arginines as genomes expanded. Insertion of arginines into their evolutionary conserved position in H2A of a small-genome organism increased linear compaction by as much as 40%, while their absence markedly diminished compaction in cells with large genomes. This effect was recapitulated in vitro with nucleosomal arrays using unmodified histones, indicating that H2A N-terminus directly modulates the chromatin fiber likely through intra- and inter-nucleosomal arginine-DNA contacts to enable tighter nucleosomal packing. Our findings reveal a novel evolutionary mechanism for regulation of chromatin compaction and may explain the frequent mutations of the H2A N-terminus in cancer.

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Author details

  1. Benjamin R Macadangdang

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Amit Oberai

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Tanya Spektor

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Oscar A Campos

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Fang Sheng

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael F Carey

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Maria Vogelauer

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Siavash K Kurdistani

    University of California, Los Angeles, Los Angeles, United States
    For correspondence
    skurdistani@mednet.ucla.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Benjamin R Macadangdang
  2. Amit Oberai
  3. Tanya Spektor
  4. Oscar A Campos
  5. Fang Sheng
  6. Michael F Carey
  7. Maria Vogelauer
  8. Siavash K Kurdistani
(2014)
Evolution of histone 2A for chromatin compaction in eukaryotes
eLife 3:e02792.
https://doi.org/10.7554/eLife.02792

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https://doi.org/10.7554/eLife.02792

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