Straussman Ravid, Nejman Deborah, Roberts Douglas, Steinfeld Israel, Blum Barak, Benvenisty Nissim, Simon Itamar, Yakhini Zohar, Cedar Howard
Department of Cellular Biochemistry and Human Genetics, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Nat Struct Mol Biol. 2009 May;16(5):564-71. doi: 10.1038/nsmb.1594. Epub 2009 Apr 19.
CpG island-like sequences are commonly thought to provide the sole signals for designating constitutively unmethylated regions in the genome, thus generating open chromatin domains within a sea of global repression. Using a new database obtained from comprehensive microarray analysis, we show that unmethylated regions (UMRs) seem to be formed during early embryogenesis, not as a result of CpG-ness, but rather through the recognition of specific sequence motifs closely associated with transcription start sites. This same system probably brings about the resetting of pluripotency genes during somatic cell reprogramming. The data also reveal a new class of nonpromoter UMRs that become de novo methylated in a tissue-specific manner during development, and this process may be involved in gene regulation. In short, we show that UMRs are an important aspect of genome structure that have a dynamic role in development.
人们普遍认为，CpG岛样序列为指定基因组中组成性未甲基化区域提供了唯一信号，从而在整体抑制的海洋中产生开放染色质结构域。通过使用从全面微阵列分析中获得的新数据库，我们发现未甲基化区域（UMR）似乎在早期胚胎发育过程中形成，不是由于CpG性质，而是通过识别与转录起始位点密切相关的特定序列基序。在体细胞重编程过程中，同一系统可能会导致多能性基因的重置。数据还揭示了一类新的非启动子UMR，它们在发育过程中以组织特异性方式从头甲基化，这一过程可能参与基因调控。简而言之，我们表明UMR是基因组结构的一个重要方面，在发育中具有动态作用。
