Function of SPOC1 (PHF13) in meiotic sex chromsome inactivation (MSCI)

SPOC1 (PHF13) 在减数分裂性染色体失活 (MSCI) 中的功能

• 批准号: 234738969
• 负责人: Professor Dr. Andreas Winterpacht
• 金额: --
• 依托单位: Humangenetisches Institut
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/234738969?language=en
• 关键词: Function; SPOC1; PHF13; meiotic; sex

During the pachytene stage of male meiosis the X- and Y-chromosomes condense into a compact structure, called the XY-body. This coincides with a vast transcriptional silencing of the heterologous, unpaired regions of the sex chromosomes. This process is called meiotic sex chromosome inactivation (MSCI). Disturbances in this process result in a breakdown of spermatogenesis. SPOC1 (PHF13) is a recently identified protein which associates with chromatin and plays a role in writing and reading of epigenetic marks. Using Spoc1-/- mice we were able to demonstrate that loss of SPOC1 results in impaired spermatogenesis and infertility. Genome wide expression studies revealed overexpression of genes on the X- and Y-chromosome during meiosis of Spoc1-/- mice. Consequently, we hypothesize that SPOC1 is involved in proper MSCI via epigenetic mechanisms. In the present proposal we intend to prove this hypothesis by means of immuncytochemical investigations and genome wide epigenetic analysis. Despite the function of SPOC1 during spermatogenesis the expected results will shed light on the (epigenetic) mechanism of MSCI, for which very limited data have been available so far.

在雄性减数分裂的粗线期，X和Y染色体凝聚成一个紧凑的结构，称为XY体。这与性染色体的异源、未配对区域的大量转录沉默相一致。这一过程被称为减数分裂性染色体失活（MSCI）。这一过程的紊乱会导致精子发生的中断。SPOC 1（PHF 13）是最近发现的一种与染色质结合的蛋白质，在表观遗传标记的书写和阅读中起作用。使用Spoc 1-/-小鼠，我们能够证明SPOC 1的缺失导致精子发生受损和不育。全基因组表达研究揭示了Spoc 1-/-小鼠减数分裂过程中X和Y染色体上基因的过度表达。因此，我们假设SPOC 1通过表观遗传机制参与适当的MSCI。在本研究中，我们打算通过免疫细胞化学研究和全基因组表观遗传学分析来证明这一假说。尽管SPOC 1在精子发生过程中的功能，预期的结果将阐明MSCI的（表观遗传）机制，到目前为止，这方面的数据非常有限。

项目成果

PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

• DOI: 10.7554/elife.10607
• 发表时间: 2016-05-25
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Chung, Ho-Ryun;Xu, Chao;Kinkley, Sarah
• 通讯作者: Kinkley, Sarah

Chromatin-Remodeling Factor SPOC1 Acts as a Cellular Restriction Factor against Human Cytomegalovirus by Repressing the Major Immediate Early Promoter

染色质重塑因子 SPOC1 通过抑制主要立即早期启动子作为抗人巨细胞病毒的细胞限制因子

• DOI: 10.1128/jvi.00342-18
• 发表时间: 2018
• 期刊: Journal of Virology
• 影响因子: 5.4
• 作者: Reichel A;Stilp AC;Scherer M;Reuter N;Lukassen S;Kasmapour B;Schreiner S;Cicin-Sain L;Winterpacht A;Stamminger T
• 通讯作者: Stamminger T