4.6 Review

Asymmetric Histone Inheritance: Establishment, Recognition, and Execution

Journal

ANNUAL REVIEW OF GENETICS
Volume 56, Issue -, Pages 113-143

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-genet-072920-125226

Keywords

epigenetic inheritance; DNA replication-coupled histone assembly; epigenetic memory; nonrandom chromatid segregation; mitotic drive; nucleosome density

Funding

  1. American Cancer Society [133950-PF-19-131-01-DMC]
  2. National Institute of General Medical Sciences/National Institutes of Health (NIH) [R35GM127075]
  3. National Institute of Child Health and Human Development/NIH [R01HD102474]
  4. Howard Hughes Medical Institute

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The discovery of biased histone inheritance in male germline stem cells of Drosophila melanogaster demonstrates a mechanism to produce two distinct daughter cells with identical genetic material. This phenomenon may be widespread and involve three steps: establishing histone asymmetry during DNA replication, recognizing sister chromatids carrying asymmetric histone information during mitosis, and executing this asymmetry in the resulting daughter cells. This review comprehensively details known factors and mechanisms involved in each step and discusses their potential contributions to cell fate decisions in multicellular organisms.
The discovery of biased histone inheritance in asymmetrically dividing Drosophila melanogaster male germline stem cells demonstrates one means to produce two distinct daughter cells with identical genetic material. This inspired further studies in different systems, which revealed that this phenomenon may be a widespread mechanism to introduce cellular diversity. While the extent of asymmetric histone inheritance could vary among systems, this phenomenon is proposed to occur in three steps: first, establishment of histone asymmetry between sister chromatids during DNA replication; second, recognition of sister chromatids carrying asymmetric histone information duringmitosis; and third, execution of this asymmetry in the resulting daughter cells. By compiling the current knowledge from diverse eukaryotic systems, this review comprehensively details and compares known chromatin factors, mitotic machinery components, and cell cycle regulators that may contribute to each of these three steps. Also discussed are potential mechanisms that introduce and regulate variable histone inheritance modes and how these different modes may contribute to cell fate decisions in multicellular organisms.

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