Uploaded October 2025 | Updated September 2026, 4 hours ago
At PacBio PRISM, Michay Diez of the Stowers Institute for Medical Research presents findings that challenge established models of gene regulation. This research explores a developmental switch in zebrafish where two distinct subtypes of 45S ribosomal RNA (rRNA) are expressed. The investigation uncovers a paradox: somatic 45S rRNA genes remain actively transcribed despite being constitutively hypermethylated, a state typically associated with gene silencing.
Using PacBio HiFi sequencing to achieve single-molecule resolution, Diez and his team validated that this hypermethylation is a genuine biological feature, not a technical artifact. The data further revealed that the transcription factor UBTF binds directly to these methylated genes in zebrafish—the opposite of its behavior in mammalian systems. These findings, powered by long-read sequencing, demonstrate that high methylation of active rRNA genes may be a common feature in teleosts, opening new avenues for understanding the complex rules of chromatin regulation.
00:00 Introduction: Zebrafish ribosomal DNA
00:33 The maternal-somatic ribosome switch
04:10 Evolutionary history of the two rRNA subtypes
07:08 Epigenetic regulation and the role of methylation
09:51 The paradox: hypermethylation and active transcription
12:30 Validating results with PacBio HiFi sequencing
15:40 UBTF binding to methylated somatic DNA
17:47 Contrasting Teleost and mammalian methylation
19:18 Future research and assembling a T2T genome
Subscribe for more insights from PacBio: youtube.com/@PacificBiosciences?sub_confirmation=1
Learn more about PacBio at pacb.com
Legal & Trademarks: Visit pacb.com/legal-and-trademarks
At PacBio PRISM, Michay Diez of the Stowers Institute for Medical Research presents findings that challenge established models of gene regulation. This research explores a developmental switch in zebrafish where two distinct subtypes of 45S ribosomal RNA (rRNA) are expressed. The investigation uncovers a paradox: somatic 45S rRNA genes remain actively transcribed despite being constitutively hypermethylated, a state typically associated with gene silencing.
Using PacBio HiFi sequencing to achieve single-molecule resolution, Diez and his team validated that this hypermethylation is a genuine biological feature, not a technical artifact. The data further revealed that the transcription factor UBTF binds directly to these methylated genes in zebrafish—the opposite of its behavior in mammalian systems. These findings, powered by long-read sequencing, demonstrate that high methylation of active rRNA genes may be a common feature in teleosts, opening new avenues for understanding the complex rules of chromatin regulation.
00:00 Introduction: Zebrafish ribosomal DNA
00:33 The maternal-somatic ribosome switch
04:10 Evolutionary history of the two rRNA subtypes
07:08 Epigenetic regulation and the role of methylation
09:51 The paradox: hypermethylation and active transcription
12:30 Validating results with PacBio HiFi sequencing
15:40 UBTF binding to methylated somatic DNA
17:47 Contrasting Teleost and mammalian methylation
19:18 Future research and assembling a T2T genome
Subscribe for more insights from PacBio: youtube.com/@PacificBiosciences?sub_confirmation=1
Learn more about PacBio at pacb.com
Legal & Trademarks: Visit pacb.com/legal-and-trademarks
