Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes
Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes
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DOI：
10.1101/gad.1416906
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发表时间：
2006-05-15
影响因子：
10.5
通讯作者：
Tilghman, Shirley M.
中科院分区：
文献类型：
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作者：
Mancini-DiNardo, Debora;Steele, Scott J. S.;Tilghman, Shirley M.
小鼠7号染色体端粒末端的印迹基因簇包含一个差异甲基化的CpG岛KvDMR，这是印迹多个基因所必需的，包括编码母体表达的胎盘特异性转录因子ASCL2、细胞周期蛋白依赖的激酶CDKN1C和钾通道KCNQ1的基因。KvDMR定位于KCNQ1内含子10，含有家系表达的非编码反义转录物Kcnq1ot1的启动子。父亲等位基因上244个碱基对的启动子缺失会导致所有被测试的沉默基因去抑制。为了区分沉默的丧失是由于转录缺失还是由于转录本身，我们通过在启动子下游插入转录停止信号来过早截断Kcnq1ot1转录本。我们发现，在父系染色体上缺乏全长Kcnq1ot1转录本会导致正常情况下父系抑制的基因表达。最后，我们证明了Kcnq1ot1转录本5‘端的5个高度保守的重复序列不是该基因印记所必需的。
The imprinted gene cluster at the telomeric end of mouse chromosome 7 contains a differentially methylated CpG island, KvDMR, that is required for the imprinting of multiple genes, including the genes encoding the maternally expressed placental-specific transcription factor ASCL2, the cyclin-dependent kinase CDKN1C, and the potassium channel KCNQ1. The KvDMR, which maps within intron 10 of Kcnq1, contains the promoter for a paternally expressed, noncoding, antisense transcript, Kcnq1ot1. A 244-base-pair deletion of the promoter on the paternal allele leads to the derepression of all silent genes tested. To distinguish between the loss of silencing as the consequence of the absence of transcription or the transcript itself, we prematurely truncated the Kcnq1ot1 transcript by inserting a transcriptional stop signal downstream of the promoter. We show that the lack of a full-length Kcnq1ot1 transcript on the paternal chromosome leads to the expression of genes that are normally paternally repressed. Finally, we demonstrate that five highly conserved repeats residing at the 5' end of the Kcnq1ot1 transcript are not required for imprinting at this locus.