| dc.identifier.uri | http://hdl.handle.net/11401/76920 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | One of the most remarkable chromatin remodeling processes occurs during the post- meiotic phase of sperm development, namely spermiogenesis. In mammals, this process results in the majority of the somatic histones being replaced with sperm-specific basic proteins called protamines, which repackage the genome into the distinctive and highly compact chromatin structure characteristic of mature sperm. This poorly understood process is not only crucial for male fertility, but also offers a unique experimental system to elucidate mechanisms of chromatin remodeling. Here I identified a critical role of Chromodomain helicase DNA binding protein 5 (Chd5) in the histone-to-protamine chromatin remodeling process. I found that Chd5 deficiency led to defective compaction of sperm chromatin and infertility in mice, mirroring the observation that low CHD5 levels correlated with male infertility in humans. I revealed that Chd5 was critical for orchestrating a cascade of molecular events required for efficient histone removal and replacement. I also discovered that Chd5 deficiency led to disruption of the homeostasis of sperm-specific basic proteins that replace histones, including transition protein 1 (Tnp1), transition protein 2 (Tnp2), protamine 1 (Prm1) and protamine 2 (Prm2), aberrant expression of which compromises fertility. These findings defined Chd5 as a multi-faceted modulator of the histone-to-protamine remodeling process, and also depicted the cascade of molecular events underlying the histone removal process during spermiogenesis, providing a guiding model for further elucidation of this elusive process of extensive chromatin remodeling. | |
| dcterms.available | 2017-09-20T16:51:26Z | |
| dcterms.contributor | Tonks, Nicholas | en_US |
| dcterms.contributor | Mills, Alea A. | en_US |
| dcterms.contributor | Stenlund, Arne | en_US |
| dcterms.contributor | Sordella, Raffaella | en_US |
| dcterms.contributor | Crawford, Howard. | en_US |
| dcterms.creator | Li, Wangzhi | |
| dcterms.dateAccepted | 2017-09-20T16:51:26Z | |
| dcterms.dateSubmitted | 2017-09-20T16:51:26Z | |
| dcterms.description | Department of Biochemistry and Cell Biology. | en_US |
| dcterms.extent | 145 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/76920 | |
| dcterms.issued | 2015-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:51:26Z (GMT). No. of bitstreams: 1
Li_grad.sunysb_0771E_11613.pdf: 5535122 bytes, checksum: 54f8ff0db72a8e0e32573cc0ed5ef8fd (MD5)
Previous issue date: 2013 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Developmental biology | |
| dcterms.subject | Chd5, chromatin remodeling, DNA damage, histone replacement, male fertility, spermatogenesis | |
| dcterms.title | The chromatin remodeler Chd5 orchestrates repackaging of the sperm genome | |
| dcterms.type | Dissertation | |
