关键词: LAD NPC TAD differentiation genome organization heterochromatin lamin nucleoporins

Mesh : Animals Oogenesis / genetics Drosophila Proteins / metabolism genetics Cell Differentiation / genetics Nuclear Pore / metabolism genetics Genome, Insect / genetics Gene Expression Regulation, Developmental / genetics Female Drosophila melanogaster / genetics Oocytes / metabolism Transcription Factors / metabolism genetics Drosophila / genetics Nuclear Pore Complex Proteins / metabolism genetics

来  源:   DOI:10.1101/gad.351402.123   PDF(Pubmed)

Abstract:
Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions.
摘要:
基因组组织可以调节基因表达并促进细胞命运转变。果蝇种系干细胞(GSCs)向卵母细胞的分化涉及异染色质和核孔复合物(NPC)介导的基因组组织变化。异染色质在分化过程中抑制生殖细胞基因,NPC将这些沉默的基因锚定到核外围,保持沉默以允许卵母细胞发育。令人惊讶的是,我们发现基因组组织也有助于NPC的形成,由转录因子Stonewall(Stwl)介导。随着GSC的分化,Stwl在沉默的和活跃的基因区室之间的边界处积累。这些边界处的Stwl在将生殖细胞基因转变为沉默状态并激活一组卵母细胞基因和核孔蛋白(Nups)中起着关键作用。分化过程中这些Nups的上调对于NPC形成和进一步的基因组组织至关重要。因此,基因组结构和NPC之间的交叉对话对于成功的细胞命运转变至关重要。
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