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<p>The precise location and functions of <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification on mammalian nuclear noncoding RNA remain largely unknown. Here we developed nuclear-m<sup>6</sup>A-label-seq to directly map human and mouse cell nuclear RNA m<sup>6</sup>A methylome at single-base resolution. Specifically, m<sup>6</sup>A modifications have been identified on abundant human γ satellite DNA II (GSATII) RNA transcripts, a type of repeat RNA, transcribed from SST1–TAR1–GSATII satellite arrays in the pericentromeric region of chromosome 9. GSATII RNA m<sup>6</sup>A positively regulates the transcription of GSATII-located satellite arrays as well as <i>trans</i>-associated peri/centromeric satellites, typically chromosome 3 centromeric higher-order repeat α satellite. Dysregulation of this circuit renders a phenotype of abnormal chromosome segregation. Mechanistic study reveals that YTHDC1 reads GSATII RNA m<sup>6</sup>A marks and recruits bromodomain protein 4 (BRD4) to promote transcriptions of the associated satellites via an m<sup>6</sup>A–YTHDC1–BRD4–H3K27ac axis. These results uncover a mechanism governing the transcription of <i>cis</i>- and <i>trans</i>-associated pericentromeric and centromeric satellites via cross-talk between epitranscriptomic and epigenomic marks.</p><p></p>

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Nuclear m6A modification regulates satellite transcription and chromosome segregation

  • 期刊论文

  • 发表日期：

    2025年5月22日

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  • Chenyang Huang,
  • Xiao Shu,
  • Siting Zhou,
  • Yujie Mi,
  • Hanxiao Bian,
  • Ting Li,
  • Tengwei Li,
  • Xiner Ying,
  • Chongguang Cheng,
  • Donghong Liu,
  • Minsong Gao,
  • Yongjian Wen,
  • Quan Ma,
  • Fengqin Wang,
  • Jie Cao,
  • Jinkai Wang,
  • Jianzhao Liu

摘要

The precise location and functions of N6-methyladenosine (m6A) modification on mammalian nuclear noncoding RNA remain largely unknown. Here we developed nuclear-m6A-label-seq to directly map human and mouse cell nuclear RNA m6A methylome at single-base resolution. Specifically, m6A modifications have been identified on abundant human γ satellite DNA II (GSATII) RNA transcripts, a type of repeat RNA, transcribed from SST1–TAR1–GSATII satellite arrays in the pericentromeric region of chromosome 9. GSATII RNA m6A positively regulates the transcription of GSATII-located satellite arrays as well as trans-associated peri/centromeric satellites, typically chromosome 3 centromeric higher-order repeat α satellite. Dysregulation of this circuit renders a phenotype of abnormal chromosome segregation. Mechanistic study reveals that YTHDC1 reads GSATII RNA m6A marks and recruits bromodomain protein 4 (BRD4) to promote transcriptions of the associated satellites via an m6A–YTHDC1–BRD4–H3K27ac axis. These results uncover a mechanism governing the transcription of cis- and trans-associated pericentromeric and centromeric satellites via cross-talk between epitranscriptomic and epigenomic marks.