Ribosomal DNA contributes to global chromatin regulation
Ribosomal DNA contributes to global chromatin regulation
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DOI：
10.1073/pnas.0906811106
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发表时间：
2009-10-20
影响因子：
11.1
通讯作者：
Maggert, Keith A.
中科院分区：
文献类型：
--
作者：
Paredes, Silvana;Maggert, Keith A.
35S核糖体RNA基因（rDNA）在许多生物中被组织为重复阵列。rRNA转录的表观遗传调控导致只有一部分拷贝被转录，这使得rDNA成为理解表观遗传染色质修饰的重要模型。我们在果蝇Y染色体的rDNA阵列中创建了一系列等位基因缺失，这些缺失影响核仁大小和形态，但不限制稳态rRNA浓度。这些rDNA缺失导致基因组中其他地方的异染色质诱导的基因沉默减少，并且rDNA缺失的程度与沉默的丧失相关。与此相一致的是，从异染色质形成所需的基因突变菌株中分离的染色体具有非常小的rDNA阵列，加强了异染色质和rDNA之间的连接。在野生型细胞中，经历自发的自然rDNA损失，我们观察到相同的rDNA损失和异染色质诱导的沉默损失之间的相关性，表明rDNA阵列的波动性可能通过正常发育和分化的表观遗传影响基因表达。我们建议，rDNA有助于异染色质和常染色质之间的平衡，在rDNA诱导或自然的改变影响这种平衡。
The 35S ribosomal RNA genes (rDNA) are organized as repeated arrays in many organisms. Epigenetic regulation of transcription of the rRNA results in only a subset of copies being transcribed, making rDNA an important model for understanding epigenetic chromatin modification. We have created an allelic series of deletions within the rDNA array of the Drosophila Y chromosome that affect nucleolus size and morphology, but do not limit steady-state rRNA concentrations. These rDNA deletions result in reduced heterochromatin-induced gene silencing elsewhere in the genome, and the extent of the rDNA deletion correlates with the loss of silencing. Consistent with this, chromosomes isolated from strains mutated in genes required for proper heterochromatin formation have very small rDNA arrays, reinforcing the connection between heterochromatin and the rDNA. In wild-type cells, which undergo spontaneous natural rDNA loss, we observed the same correlation between loss of rDNA and loss of heterochromatin-induced silencing, showing that the volatility of rDNA arrays may epigenetically influence gene expression through normal development and differentiation. We propose that the rDNA contributes to a balance between heterochromatin and euchromatin in the nucleus, and alterations in rDNA-induced or natural-affect this balance.