Kemp James P, Geisler Mark S, Hoover Mia, Cho Chun-Yi, O'Farrell Patrick H, Marzluff William F, Duronio Robert J
Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC, 27599 USA.
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599 USA.
Mol Biol Cell. 2025 May 21:mbcE25050212. doi: 10.1091/mbc.E25-05-0212.
Coordinated expression of replication-dependent (RD) histones genes occurs within the Histone Locus Body (HLB) during S phase, but the molecular steps in transcription that are cell cycle regulated are unknown. We report that RNA Pol II promotes HLB formation and is enriched in the HLB outside of S phase, including G1-arrested cells that do not transcribe RD histone genes. In contrast, the transcription elongation factor Spt6 is enriched in HLBs only during S phase. Proliferating cells in the wing and eye primordium express full-length histone mRNAs during S phase but express only short nascent transcripts in cells in G1 or G2 consistent with these transcripts being paused and then terminated. Full-length transcripts are produced when Cyclin E/Cdk2 is activated as cells enter S phase. Thus, activation of transcription elongation by Cyclin E/Cdk2 and not recruitment of RNA pol II to the HLB is the critical step that links histone gene expression to cell cycle progression. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].
复制依赖性（RD）组蛋白基因的协调表达在S期于组蛋白基因座体（HLB）内发生，但转录过程中受细胞周期调控的分子步骤尚不清楚。我们报告称，RNA聚合酶II促进HLB形成，并且在S期之外的HLB中富集，包括不转录RD组蛋白基因的G1期阻滞细胞。相比之下，转录延伸因子Spt6仅在S期在HLB中富集。翅和眼原基中的增殖细胞在S期表达全长组蛋白mRNA，但在G1期或G2期的细胞中仅表达短的新生转录本，这与这些转录本被暂停然后终止一致。当细胞进入S期细胞周期蛋白E/细胞周期蛋白依赖性激酶2（Cyclin E/Cdk2）被激活时产生全长转录本。因此，细胞周期蛋白E/细胞周期蛋白依赖性激酶2激活转录延伸而非RNA聚合酶II募集到HLB是将组蛋白基因表达与细胞周期进程联系起来的关键步骤。
