High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner
High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner
复制标题
DOI：
10.1074/jbc.m113.463315
复制
发表时间：
2013-06-07
影响因子：
4.8
通讯作者：
Bustin, Michael
中科院分区：
文献类型：
--
作者：
Kugler, Jamie E.;Horsch, Marion;Bustin, Michael
大多数脊椎动物细胞的细胞核含有高迁移率族N（HMGN）蛋白家族的成员，其特异性结合核小体核心颗粒并影响染色质结构和功能，包括转录。在这里，我们研究的生物学作用，这个蛋白质家族的表型和组织转录谱缺乏功能性HMGN变异小鼠的系统分析。Hmgn 1（tm 1/tm 1），Hmgn 3（tm 1/tm 1）和Hmgn 5（tm 1/tm 1）小鼠及其野生型同窝小鼠的表型分析与标准化测试电池发现变异特异性异常。在每个Hmgn（tm 1/tm 1）系中的四个不同组织的基因表达分析揭示了在不同组织中受特定变体影响的基因之间的非常小的重叠。通路分析表明，HMGN变体的丢失微妙地影响了特定生物过程中许多基因的表达。我们得出结论，在整个生物体的生物学框架内，HMGN以组织和HMGN变体特异性方式调节细胞转录谱的保真度。
The nuclei of most vertebrate cells contain members of the high mobility group N (HMGN) protein family, which bind specifically to nucleosome core particles and affect chromatin structure and function, including transcription. Here, we study the biological role of this protein family by systematic analysis of phenotypes and tissue transcription profiles in mice lacking functional HMGN variants. Phenotypic analysis of Hmgn1(tm1/tm1), Hmgn3(tm1/tm1), and Hmgn5(tm1/tm1) mice and their wild type littermates with a battery of standardized tests uncovered variant-specific abnormalities. Gene expression analysis of four different tissues in each of the Hmgn(tm1/tm1) lines reveals very little overlap between genes affected by specific variants in different tissues. Pathway analysis reveals that loss of an HMGN variant subtly affects expression of numerous genes in specific biological processes. We conclude that within the biological framework of an entire organism, HMGNs modulate the fidelity of the cellular transcriptional profile in a tissue- and HMGN variant-specific manner.