Widespread Enhancer Dememorization and Promoter Priming during Parental-to-Zygotic Transition

Mol Cell. 2018 Nov 15;72(4):673-686.e6. doi: 10.1016/j.molcel.2018.10.017.

Abstract

The epigenome plays critical roles in controlling gene expression and development. However, how the parental epigenomes transit to the zygotic epigenome in early development remains elusive. Here we show that parental-to-zygotic transition in zebrafish involves extensive erasure of parental epigenetic memory, starting with methylating gametic enhancers. Surprisingly, this occurs even prior to fertilization for sperm. Both parental enhancers lose histone marks by the 4-cell stage, and zygotic enhancers are not activated until around zygotic genome activation (ZGA). By contrast, many promoters remain hypomethylated and, unexpectedly, acquire histone acetylation before ZGA at as early as the 4-cell stage. They then resolve into either activated or repressed promoters upon ZGA. Maternal depletion of histone acetyltransferases results in aberrant ZGA and early embryonic lethality. Finally, such reprogramming is largely driven by maternal factors, with zygotic products mainly contributing to embryonic enhancer activation. These data reveal widespread enhancer dememorization and promoter priming during parental-to-zygotic transition.

Keywords: early embryo development; epigenetic memory removal; epigenetic reprogramming; histone modifications; parental-to-zygotic transition; zebrafish epigenome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • DNA Methylation / genetics
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / physiology
  • Epigenomics
  • Gene Expression Regulation, Developmental / genetics
  • Genome / genetics
  • Histone Code / genetics*
  • Histone Code / physiology*
  • Histones / genetics
  • Male
  • Oocytes
  • Promoter Regions, Genetic / genetics
  • Protein Processing, Post-Translational
  • Regulatory Sequences, Nucleic Acid / genetics
  • Spermatozoa
  • Transcription, Genetic / genetics
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins
  • Zygote / physiology

Substances

  • Histones
  • Zebrafish Proteins