权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation of chromatin remodeling during spermiogenesis

精子发生过程中染色质重塑的调节

基本信息

批准号：
8974424
负责人：
PRABHAKARA P REDDI
金额：
$ 7.85万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8974424
关键词：
Accounting Acrosome Adult Affect Applications Grants Archives Assisted Reproductive Technology Binding Biological Models Birth Breeding Bypass CCCTC-binding factor Cell Nucleus Cells ChIP-seq Chromatin Complex Conceptions Congenital Abnormality Couples DNA-Binding Proteins Defect Developed Countries Development Disease Embryonic Development Epigenetic Process European Event Feasibility Studies Fertility Fertilization Fetal Growth Retardation Flagella Genes Genetic Genetic Transcription Genome Germ Cells Germ Lines Health Histones Human Immunohistochemistry Infertility Injection of therapeutic agent Intercistronic Region Knock-out Knockout Mice Lead Life LoxP-flanked allele Male Infertility Malignant Childhood Neoplasm Methods Modeling Molecular Mus Mutant Strains Mice Natural Selections Nuclear Nuclear Proteins Phase Physical condensation Physical shape Pilot Projects Play Preparation Process Protamines Proteins Regulation Reproductive Health Risk Role Sperm Maturation Spermatids Spermatogenesis Spermiogenesis Spontaneous abortion Staging Technology Testing Testis Time Treatment Factor United States Ursidae Family Validation Work Zinc Fingers age group base chromatin remodeling egg embryonic stem cell gene repression genome-wide imprint improved insight knockout gene male mouse model novel promoter reproductive research study screening sperm cell technology development transcription factor

项目摘要

DESCRIPTION (provided by applicant): The differentiation of round spermatids into spermatozoa, known as spermiogenesis, is a complex process involving the formation of the acrosome, the flagellum, and condensation of the nucleus. In preparation for condensation, the spermatid nucleus undergoes dramatic chromatin remodeling including genome-wide cessation of transcription, dismantling of the nucleosomal organization, and histone to protamine transition. This process is unique to the male germ line. Mouse models have shown that defects in nuclear condensation lead to male infertility; however, the mechanisms regulating this complex genome-wide process are not well understood. Our working hypothesis is that the genome organizer protein CTCF coordinates the chromatin remodeling events accompanying spermatid differentiation. The evolutionarily conserved eleven zinc finger protein CCCTC-binding factor (CTCF) is exclusively expressed within the round and early elongating spermatids in mice, coinciding with transcriptional shutdown and the onset of histone replacement. In this pilot, feasibility grant proposal we will test the hypotheses that: 1) CTCF functions as a transcription factor as well as an organizer of spermatid genome to facilitate chromatin remodeling and 2) CTCF is essential for the completion of spermatogenesis and male fertility. We will perform ChIP-seq to determine genome-wide occupancy of CTCF in round spermatids and generate CTCF conditional knockout mice using the Cre-loxP technology to test the requirement of CTCF for spermatogenesis and male fertility. CTCF is an ideal candidate for this role because it is a multifunctional DNA binding protein with diverse roles including that of a chromatin organizer. Floxed CTCF mice as well as the male germ cell-specific cre-deleter strain (Stra8-iCre) are readily available. This proposal will explore the role of CTCF in male fertility fr the first time. Infertility affects 1 in 6 couples in the reproductive age group, with the male facor accounting for 50% of those cases. If depletion of CTCF causes sperm maturation arrest, this study will provide a novel mouse model for male infertility. Given the role that CTCF plays in establishing and / or maintaining epigenetic marks, the proposed knockout mouse may be a useful model to understand the risks involved in Assisted Reproductive Technology using incompletely developed spermatids or sperm. Thus, the studies are highly significant from the point of view of male reproductive health.