Abstract
Histone modifications are important epigenetic features of chromatin that must be replicated faithfully. However, the molecular mechanisms required to duplicate and maintain histone modification patterns in chromatin remain to be determined. Here, we show that the introduction of histone modifications into newly deposited nucleosomes depends upon their location in the chromosome. In Saccharomyces cerevisiae, newly deposited nucleosomes consisting of newly synthesized histone H3-H4 tetramers are distributed throughout the entire chromosome. Methylation of lysine 4 on histone H3 (H3-K4), a hallmark of euchromatin, is introduced into these newly deposited nucleosomes, regardless of whether the neighboring preexisting nucleosomes harbor the K4 mutation in histone H3. Furthermore, if the heterochromatin-binding protein Sir3 is unavailable during DNA replication, histone H3-K4 methylation is introduced onto newly deposited nucleosomes in telomeric heterochromatin. Thus, a conservative distribution model most accurately explains the inheritance of histone modifications because the location of histones within euchromatin or heterochromatin determines which histone modifications are introduced.
Highlights
The heritability of cell-specific gene regulation maintains that chromatin structures must be propagated across cell generations [1,2]
If a newly deposited nucleosome consists of a hybrid of new and old histone H3 molecules, the Flag-tagged H3 would be acetylated, and the untagged H3 should be largely unacetylated on K56 (Fig. 1A: Semi-conservative distribution model)
We expected that K56 on histone H3 molecules in newly deposited nucleosomes would remain acetylated after degradation of Hst4-aid by treatment with indole acetic acid (IAA) from the G1 until the G2/M phase (Fig. 1B)
Summary
The heritability of cell-specific gene regulation maintains that chromatin structures must be propagated across cell generations [1,2]. The basic unit of chromatin packaging, the nucleosome, consists of 147 bp of DNA wrapped around an octamer of the core histones H2A, H2B, H3 and H4. Because histone modifications influence several DNA-associated processes, including replication and transcription, these modifications can impact the integrity of the chromatin structure and epigenetic inheritance [2]. Chromatin is categorized into two transcriptionally distinct regions: euchromatin and heterochromatin. Heterochromatin, which is thought to be regions that are transcriptionally silent, is found at telomeres, the silent mating type loci (HMLa and HMRa) and ribosomal DNA repeats in yeast. The high-fidelity inheritance of epigenetic chromatin structures across cell generations is required for the correct duplication of histone modification patterns from the mother chromosome to the two daughter chromosomes. The molecular mechanism of inheritance of epigenetic chromatin structures remains to be determined
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