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<p>In all eukaryotes, DNA replication is coupled to histone synthesis to coordinate chromatin packaging of the genome. Canonical histone genes coalesce in the nucleus into the histone locus body (HLB), where gene transcription and 3′ mRNA processing occurs. Both histone gene transcription and mRNA stability are reduced when DNA replication is inhibited, implying that the HLB senses the rate of DNA synthesis. In <i>Drosophila</i> <i>melanogaster</i>, the S-phase-induced histone genes are tandemly repeated in an ~100 copy array, whereas, in humans, these histone genes are scattered. In both organisms, these genes coalesce into HLBs. Here, we use a transgenic histone gene reporter and RNA interference in <i>Drosophila</i> to identify canonical H4 histone as a unique repressor of histone synthesis during the G2 phase in germline cells. Using cytology and CUT&amp;Tag chromatin profiling, we find that histone H4 uniquely occupies histone gene promoters in both <i>Drosophila</i> and human cells. Our results suggest that repression of histone genes by soluble histone H4 is a conserved mechanism that coordinates DNA replication with histone synthesis in proliferating cells.</p>

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Cell-cycle-dependent repression of histone gene transcription by histone H4

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月5日

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  • Kami Ahmad,
  • Matt Wooten,
  • Brittany N. Takushi,
  • Velinda Vidaurre,
  • Xin Chen,
  • Steven Henikoff

摘要

In all eukaryotes, DNA replication is coupled to histone synthesis to coordinate chromatin packaging of the genome. Canonical histone genes coalesce in the nucleus into the histone locus body (HLB), where gene transcription and 3′ mRNA processing occurs. Both histone gene transcription and mRNA stability are reduced when DNA replication is inhibited, implying that the HLB senses the rate of DNA synthesis. In Drosophila melanogaster, the S-phase-induced histone genes are tandemly repeated in an ~100 copy array, whereas, in humans, these histone genes are scattered. In both organisms, these genes coalesce into HLBs. Here, we use a transgenic histone gene reporter and RNA interference in Drosophila to identify canonical H4 histone as a unique repressor of histone synthesis during the G2 phase in germline cells. Using cytology and CUT&Tag chromatin profiling, we find that histone H4 uniquely occupies histone gene promoters in both Drosophila and human cells. Our results suggest that repression of histone genes by soluble histone H4 is a conserved mechanism that coordinates DNA replication with histone synthesis in proliferating cells.