| dc.identifier.uri | http://hdl.handle.net/11401/77614 | |
| 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 | Neural stem/progenitor cells (NSCs) in the mammalian brain are multipotent progenitor cells that give rise to the major neural lineages such as neurons, oligodendrocytes and astrocytes. Execution of precise spatiotemporal cell fate decisions of NSCs is regulated by cell type-specific gene expression programs. The role of chromatin remodeling proteins in cell fate decisions is not well understood. Here I present evidence that Chromodomain helicase DNA binding protein 5 (Chd5) facilitates tri-methylation of lysine 27 of histone H3 to modulate the repressive mark H3K27me3, through which neural-specific gene expression programs are specified. Chd5-deficient NSCs have aberrant enrichment of the CD24Low neuronal progenitor population, accompanied by altered cellular properties and augmented expression of NSC markers. Upon differentiation, Chd5-deficient cells generate more astrocytes at the expense of neurons. Chd5 deficiency leads to global gene expression changes and the marked reduction of H3K27me3. Importantly, ectopic expression of Chd5 enhances H3K27me3 and induces neurogenesis, effectively rescuing the cell fate defects of Chd5-deficient NSCs. Lastly, Chd5 functionally interacts with the H3K27me3-specific histone demethylase Utx. These findings underscore the importance of Chd5-mediated regulation of H3K27me3 during differentiation of NSCs and define a novel Chd5-Utx axis that is a crucial determinant of cell fate decisions in the developing mammalian brain. | |
| dcterms.available | 2017-09-20T16:53:01Z | |
| dcterms.contributor | Mills, Alea A | en_US |
| dcterms.contributor | Futcher, Bruce | en_US |
| dcterms.contributor | Stillman, Bruce | en_US |
| dcterms.contributor | Vakoc, Christopher | en_US |
| dcterms.contributor | Zheng, Hongwu. | en_US |
| dcterms.creator | Hwang, Dong-Woo | |
| dcterms.dateAccepted | 2017-09-20T16:53:01Z | |
| dcterms.dateSubmitted | 2017-09-20T16:53:01Z | |
| dcterms.description | Department of Genetics. | en_US |
| dcterms.extent | 120 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/77614 | |
| dcterms.issued | 2015-05-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:53:01Z (GMT). No. of bitstreams: 1
Hwang_grad.sunysb_0771E_12424.pdf: 36983712 bytes, checksum: 217007eb98b073757b1c8982a2ad178e (MD5)
Previous issue date: 2015 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Chromatin remodeler, Histone modification, Neural cell fate | |
| dcterms.subject | Cellular biology | |
| dcterms.title | The chromatin remodeler Chd5 regulates neural cell fate through the histone demethylase Utx | |
| dcterms.type | Dissertation | |
