c-MYC coordinately regulates ribosomal gene chromatin remodeling and Pol I availability during granulocyte differentiation.
c-MYC coordinately regulates ribosomal gene chromatin remodeling and Pol I availability during granulocyte differentiation.
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C-MYC协调调节核糖体染色质重塑和粒细胞分化过程中的pol I可用性。
DOI：
10.1093/nar/gkq1205
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发表时间：
2011-04
影响因子：
14.9
通讯作者：
McArthur GA
中科院分区：
文献类型：
--
作者：
Poortinga G;Wall M;Sanij E;Siwicki K;Ellul J;Brown D;Holloway TP;Hannan RD;McArthur GA
在粒细胞分化过程中，通过RNA聚合酶I （Pol I）下调核糖体RNA （rRNA）基因（rDNA）转录需要c-MYC的缺失。在这里，我们证明了Pol I装载到rDNA上的大量减少，伴随着MYC靶基因上游结合因子（UBF）的耗尽以及从表观遗传活性到沉默rDNA的转换伴随着MYC的减少。我们假设MYC可能通过直接调节Pol I转录装置的多个组分来协调这些机制。通过基因表达阵列，我们确定了Pol I因子的一个“调控子”，该调控子在分化过程中下调，并在MYC-ER转基因激活后在分化的粒细胞中重新诱导。该调控包括新的c-MYC靶基因rn3和POLR1B。尽管粒细胞分化过程中MYC的强制表达足以增加活性rRNA基因的数量，但其在终末分化细胞中的激活并未改变活性基因与非活性基因的比例，尽管rDNA转录增加。因此，在粒细胞分化过程中，c-MYC通过核心Pol I因子的转录调控和活性rRNA基因数量的表观遗传调控来动态控制rDNA转录。
Loss of c-MYC is required for downregulation of ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) during granulocyte differentiation. Here, we demonstrate a robust reduction of Pol I loading onto rDNA that along with a depletion of the MYC target gene upstream binding factor (UBF) and a switch from epigenetically active to silent rDNA accompanies this MYC reduction. We hypothesized that MYC may coordinate these mechanisms via direct regulation of multiple components of the Pol I transcription apparatus. Using gene expression arrays we identified a ‘regulon’ of Pol I factors that are both downregulated during differentiation and reinduced in differentiated granulocytes upon activation of the MYC-ER transgene. This regulon includes the novel c-MYC target genes RRN3 and POLR1B. Although enforced MYC expression during granulocyte differentiation was sufficient to increase the number of active rRNA genes, its activation in terminally differentiated cells did not alter the active to inactive gene ratio despite increased rDNA transcription. Thus, c-MYC dynamically controls rDNA transcription during granulocytic differentiation through the orchestrated transcriptional regulation of core Pol I factors and epigenetic modulation of number of active rRNA genes.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.3
作者：
Heber, Steffen;Sick, Beate
通讯作者：
Sick, Beate
影响因子：
21.3
作者：
Grewal, SS;Li, L;Edgar, BA
通讯作者：
Edgar, BA
影响因子：
8
作者：
Hoffman, B;Amanullah, A;Liebermann, DA
通讯作者：
Liebermann, DA
影响因子：
16
作者：
Lawrence, RJ;Earley, K;Pikaard, CS
通讯作者：
Pikaard, CS