Tissue-specific expression of histone H3 variants diversified after species separation.
Tissue-specific expression of histone H3 variants diversified after species separation.
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DOI：
10.1186/s13072-015-0027-3
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发表时间：
2015
影响因子：
3.9
通讯作者：
Ohkawa Y
中科院分区：
文献类型：
--
作者：
Maehara K;Harada A;Sato Y;Matsumoto M;Nakayama KI;Kimura H;Ohkawa Y
合适的组蛋白变体选择性地掺入染色质中对于基因组功能的调节是至关重要的。虽然许多组蛋白变体已被确定，但尚未编制完整的列表。我们使用经典组蛋白序列通过计算机杂交筛选小鼠、大鼠和人类基因组。在小鼠基因组中，我们鉴定了14个未表征的H3基因，其中13个与H3.3相似，并且没有人类或大鼠对应物，并且一个与人类睾丸特异性H3变体H3 T/H3.4相似，并且具有大鼠Parkinson。尽管这些基因中的一些先前被注释为假基因，但通过对转录物的3′-UTR区域进行测序证实了它们的组织特异性表达。某些新的变体也通过质谱法在蛋白质水平上检测到。当在小鼠C2 C12细胞中表达为GFP标记的版本时，一些变体稳定地掺入染色质中，并且大多数变体的全基因组分布与H3.3的分布相似。此外，H3变体在染色质中的强制表达导致细胞分化后的交替基因表达模式。我们全面鉴定和表征了与已知组蛋白H3相比编码高度保守氨基酸序列的新型小鼠H3变体基因。我们推测，物种分离后获得的H3变体的多样性在调节个体物种的组织特异性基因表达中发挥了作用。它们的生物相关性和涉及假基因多样化的进化方面将通过进一步的功能分析来解决。本文的在线版本（doi：10.1186/s13072-015-0027-3）包含补充材料，可供授权用户使用。
The selective incorporation of appropriate histone variants into chromatin is critical for the regulation of genome function. Although many histone variants have been identified, a complete list has not been compiled. We screened mouse, rat and human genomes by in silico hybridization using canonical histone sequences. In the mouse genome, we identified 14 uncharacterized H3 genes, among which 13 are similar to H3.3 and do not have human or rat counterparts, and one is similar to human testis-specific H3 variant, H3T/H3.4, and had a rat paralog. Although some of these genes were previously annotated as pseudogenes, their tissue-specific expression was confirmed by sequencing the 3′-UTR regions of the transcripts. Certain new variants were also detected at the protein level by mass spectrometry. When expressed as GFP-tagged versions in mouse C2C12 cells, some variants were stably incorporated into chromatin and the genome-wide distributions of most variants were similar to that of H3.3. Moreover, forced expression of H3 variants in chromatin resulted in alternate gene expression patterns after cell differentiation. We comprehensively identified and characterized novel mouse H3 variant genes that encoded highly conserved amino acid sequences compared to known histone H3. We speculated that the diversity of H3 variants acquired after species separation played a role in regulating tissue-specific gene expression in individual species. Their biological relevance and evolutionary aspect involving pseudogene diversification will be addressed by further functional analysis. The online version of this article (doi:10.1186/s13072-015-0027-3) contains supplementary material, which is available to authorized users.