Maintenance of cell fates and regulation of the histone variant H3.3 by TLK kinase in Caenorhabditis elegans

Maintenance of cell fates and regulation of the histone variant H3.3 by TLK kinase in Caenorhabditis elegans
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DOI：
10.1242/bio.038448
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发表时间：
2019-01
期刊：
Biology Open
影响因子：
2.4
通讯作者：
Yukimasa Shibata;Y. Seki;K. Nishiwaki
Yukimasa Shibata;Y. Seki;K. Nishiwaki
中科院分区：
生物学4区
文献类型：
--
作者：
Yukimasa Shibata;Y. Seki;K. Nishiwaki

文献摘要

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摘要细胞命运维持对于保持组织形成和功能所必需的细胞类型的多样性是重要的。我们先前表明，乙酰化组蛋白结合蛋白BET-1通过招募组蛋白变体H2A.z来维持细胞命运。在这里，我们报告秀丽隐杆线虫TLK-1和组蛋白H3伴侣CAF 1防止组蛋白变体H3.3的积累。此外，TLK-1和CAF 1通过抑制诱导细胞命运特化的转录因子的异位表达来维持细胞命运。遗传分析表明TLK-1和BET-1在平行途径中起作用。在tlk-1突变体中，SIN-3的丢失，促进组蛋白乙酰化，抑制细胞命运维持的缺陷依赖于MYST家族组蛋白乙酰转移酶MYS-2和BET-1的方式。sin-3突变也抑制异常的H3.3掺入。因此，我们提出了一个假设，组蛋白变体的调节和相互作用通过调节选择基因在细胞命运维持中起着至关重要的作用。总结：组蛋白H3伴侣CAF 1通过抑制细胞命运指定转录因子基因的异位表达来维持细胞命运。组蛋白变体H3.3的积累与细胞命运维持缺陷相关。
ABSTRACT Cell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report that Caenorhabditis elegans TLK-1 and the histone H3 chaperone CAF1 prevent the accumulation of histone variant H3.3. In addition, TLK-1 and CAF1 maintain cell fate by repressing ectopic expression of transcription factors that induce cell-fate specification. Genetic analyses suggested that TLK-1 and BET-1 act in parallel pathways. In tlk-1 mutants, the loss of SIN-3, which promotes histone acetylation, suppressed a defect in cell-fate maintenance in a manner dependent on MYST family histone acetyltransferase MYS-2 and BET-1. sin-3 mutation also suppressed abnormal H3.3 incorporation. Thus, we propose a hypothesis that the regulation and interaction of histone variants play crucial roles in cell-fate maintenance through the regulation of selector genes. Summary: Histone H3 chaperone CAF1 maintains cell fate by repressing ectopic expression of genes for cell fate-specifying transcription factors. Accumulation of histone variant H3.3 correlates with defects in cell-fate maintenance.