Abstract
Human liver cancer is the cancer commonly seen clinically. The transcription of ribosomal DNA (rDNA) is a critical step for cells, and epigenetic marks such as post-translational histone modifications have been involved in the regulation of rDNA transcription. But less is known about the pathogenesis of the liver cancers concerning the rDNA transcription regulation. Here we aligned the ChIP-seq data of histone modification markers and CTCF to the human genome assembly which contains a single rDNA repeat in human liver cancer cell and validated their distribution with ChIP-QPCR. Human liver cancer cell possesses a higher enrichment of H3K4me1 and H3K27me3 at ~28 kb within the intergenic spacer (IGS) of rDNA and a higher enrichment of H3K4me3 and H3K27ac upstream of TSS. Furtherly, we studied whether UBF could affect histone modification markers and CTCF at rDNA in human liver cancer cell. UBF depletion leads to a decrease of gene activation mark H3K4me3 across the rDNA promoter. And other histone modification marks and CTCF were not altered after UBF depletion. Taken together, our data showed a high resolution map of histone modification marks at rDNA in human liver cancer cell and provide novel evidence to decipher chromatin-mediated regulation of rDNA in liver cancer.
Highlights
DNA methylation mediated by NoRC has been involved in the repression of ribosomal DNA (rDNA) transcription[16] and has been shown to decrease Upstream Binding Factor (UBF) binding to the rDNA promoter[17]
We aligned Chromatin Immunoprecipitation (ChIP)-seq data of CTCF from human liver cancer cell HepG2 to HG19_plus_rDNA and we have discovered that in human hepatic cancer cells, CTCF was highly enriched at the 3′ end of human ribosomal DNA just upstream of TSS (Fig. 7A,B)
As previous studies have suggested that rDNA transcription by RNA Polymerase I is tightly linked to cancerology[9] and epigenetic mechanisms are involved in the control of transcriptional activity of rRNA genes, in particular, histone modifications are a key issue to mediate the regulation of rDNA transcription
Summary
DNA methylation mediated by NoRC has been involved in the repression of rDNA transcription[16] and has been shown to decrease Upstream Binding Factor (UBF) binding to the rDNA promoter[17]. Increasing evidences suggest a regulational machinery exists to prevent the inappropriate transcription as human ribosomal DNA is organized into Nucleolar Organizing Regions (NORs) which are tandemly repeated. Such a mechanism could be involving insulator elements, the discrete transcriptional units are generally demarcated and the leaky transcription was prevented by insulator elements[19]. We report the presence of CTCF, an insulator-binding protein, at the rDNA space promoter in human liver cancer cell. Our studies showed for the first time a high-resolution map of histone modification marks and CTCF at rDNA in human liver cancer cell, and give evidence for future research of chromatin-mediated regulation of rDNA in liver cancer
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