Abstract:
:The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Xie Q,Li C,Song X,Wu L,Jiang Q,Qiu Z,Cao H,Yu K,Wan C,Li J,Yang F,Huang Z,Niu B,Jiang Z,Zhang Tdoi
10.1093/nar/gkw1208subject
Has Abstractpub_date
2017-03-17 00:00:00pages
2472-2489issue
5eissn
0305-1048issn
1362-4962pii
gkw1208journal_volume
45pub_type
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