Transcriptional Silencing of the X-chromosome

X 染色体的转录沉默

• 批准号: 7055733
• 负责人: Montserrat C Anguera
• 金额: $ 4.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-15 至 2007-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055733
• 关键词: early embryonic stage; embryonic stem cell; epigenetics; gene expression profiling; gene induction /repression; genetic transcription; genomic imprinting; laboratory mouse; postdoctoral investigator; sex chromosomes; sperm

DESCRIPTION (provided by applicant): Alterations in epigenetically-regulated gene expression are critical determinants for oncogenesis, yet the molecular details involved in epigenetic programming and imprinting are not well understood. X-chromosome inactivation (XCI) is an epigenetic event where imprinting triggers transcriptional silencing of the X for equal gene dosage in female cells. The molecular details regulating XCI in the early female embryo are not well understood, and the transcriptional status of X in the preimplantation embryo has recently become a controversial topic in the field. New evidence indicates that the paternal X (XP) is transcriptionally silent in the early embryo, suggesting that the embryo may have inherited a transcriptionally silent XP with silence originating during spermatogenesis. This research proposal will determine whether a continuum of XP transcriptional silence (from spermatogenesis into the fertilized zygote) exists. The transcriptional status of X and expression levels of various X-linked genes will be determined in post-meiotic spermatids and at different developmental stages in the pre-implantation embryo. This research will provide a foundation for future investigations into epigenetically-regulated chromosomal silencing mechanisms.

描述（由申请人提供）：表观遗传调控基因表达的改变是肿瘤发生的关键决定因素，但表观遗传编程和印记中涉及的分子细节尚不清楚。 X 染色体失活 (XCI) 是一种表观遗传事件，其中印记触发 X 的转录沉默，从而在雌性细胞中获得相同的基因剂量。早期雌性胚胎中调节XCI的分子细节尚不清楚，而植入前胚胎中X的转录状态最近已成为该领域的一个有争议的话题。新的证据表明，父系 X (XP) 在早期胚胎中是转录沉默的，这表明胚胎可能继承了转录沉默的 XP，其沉默源于精子发生过程。该研究计划将确定 XP 转录沉默的连续体（从精子发生到受精卵）是否存在。 X的转录状态和各种X连锁基因的表达水平将在减数分裂后的精细胞和植入前胚胎的不同发育阶段确定。这项研究将为未来研究表观遗传调控的染色体沉默机制奠定基础。