泛素连接酶 HR6B 在维持小鼠精母细胞和精子细胞中的 X 染色体沉默中是必需的。

The ubiquitin-conjugating enzyme HR6B is required for maintenance of X chromosome silencing in mouse spermatocytes and spermatids.

机构信息

Department of Reproduction and Development Erasmus MC, Rotterdam, The Netherlands.

出版信息

BMC Genomics. 2010 Jun 10;11:367. doi: 10.1186/1471-2164-11-367.

Abstract

BACKGROUND

The ubiquitin-conjugating enzyme HR6B is required for spermatogenesis in mouse. Loss of HR6B results in aberrant histone modification patterns on the trancriptionally silenced X and Y chromosomes (XY body) and on centromeric chromatin in meiotic prophase. We studied the relationship between these chromatin modifications and their effects on global gene expression patterns, in spermatocytes and spermatids.

RESULTS

HR6B is enriched on the XY body and on centromeric regions in pachytene spermatocytes. Global gene expression analyses revealed that spermatid-specific single- and multicopy X-linked genes are prematurely expressed in Hr6b knockout spermatocytes. Very few other differences in gene expression were observed in these cells, except for upregulation of major satellite repeat transcription. In contrast, in Hr6b knockout spermatids, 7298 genes were differentially expressed; 65% of these genes was downregulated, but we observed a global upregulation of gene transcription from the X chromosome. In wild type spermatids, approximately 20% of the single-copy X-linked genes reach an average expression level that is similar to the average expression from autosomes.

CONCLUSIONS

Spermatids maintain an enrichment of repressive chromatin marks on the X chromosome, originating from meiotic prophase, but this does not interfere with transcription of the single-copy X-linked genes that are reactivated or specifically activated in spermatids. HR6B represses major satellite repeat transcription in spermatocytes, and functions in the maintenance of X chromosome silencing in spermatocytes and spermatids. It is discussed that these functions involve modification of chromatin structure, possibly including H2B ubiquitylation.

摘要

背景

泛素连接酶 HR6B 在小鼠的精子发生中是必需的。HR6B 的缺失导致转录沉默的 X 和 Y 染色体(XY 体)以及减数分裂前期的着丝粒染色质上出现异常的组蛋白修饰模式。我们研究了这些染色质修饰之间的关系及其对精母细胞和精子中的全局基因表达模式的影响。

结果

HR6B 在精母细胞的 XY 体和着丝粒区域富集。全局基因表达分析显示,X 连锁的单拷贝和多拷贝基因在 Hr6b 敲除的精母细胞中过早表达。这些细胞中除了主要卫星重复转录上调外,观察到的其他基因表达差异很少。相比之下,在 Hr6b 敲除的精子中,有 7298 个基因差异表达;这些基因中有 65%下调,但我们观察到 X 染色体上的基因转录整体上调。在野生型精子中,大约 20%的单拷贝 X 连锁基因达到与常染色体平均表达水平相似的平均表达水平。

结论

精子保持来自减数分裂前期的 X 染色体上的抑制性染色质标记的富集,但这并不干扰重新激活或在精子中特异性激活的单拷贝 X 连锁基因的转录。HR6B 抑制精母细胞中的主要卫星重复转录,并在精母细胞和精子中维持 X 染色体沉默。讨论认为这些功能涉及染色质结构的修饰,可能包括 H2B 泛素化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/477c/3091626/b9732a443e8d/1471-2164-11-367-1.jpg

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