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Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland
Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland
Electronic Thesis and Dissertation Repository
ATRX is an ATP-dependent chromatin remodeler required to safeguard genomic integrity. Conditional deletion of Atrx in the mouse embryonic forebrain and anterior pituitary in AtrxFoxg1Cre mice phenocopies mouse models of progeria which display increased DNA damage, coupled with reduced lifespan, growth and subcutaneous fat. These mice also have severely low circulating levels of insulin like growth factor 1 (IGF-1) and (T4) which have been reported in models of premature aging. Based on evidence that Igf1 is activated by the ligand-bound thyroid hormone receptor, I tested whether T4 supplementation could restore IGF-1 levels and ameliorate premature aging phenotypes in Atrx …
Atrx Regulates H3.3 Incorporation And Gene Expression At G-Rich Ancestral Pseudoautosomal Genes, Michael A. Levy
Atrx Regulates H3.3 Incorporation And Gene Expression At G-Rich Ancestral Pseudoautosomal Genes, Michael A. Levy
Electronic Thesis and Dissertation Repository
Mutations in the ATRX gene cause alpha thalassaemia mental retardation, X linked, or can enable cancer progression. ATRX encodes a Swi2/Snf2 chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. The aim of this study was to determine the role of ATRX in the regulation of gene expression. I identified the ancestral pseudoautosomal region (aPAR) genes as some of the most downregulated genes throughout forebrain development. The PARs are homologous regions located at the ends of the X and Y chromosomes, and are rich in repetitive sequences and GC content. However, mouse PAR …
Regulation Of Imprinted Genes In The Brain By The Atrx Chromatin Remodeling Protein, Kristin D. Kernohan
Regulation Of Imprinted Genes In The Brain By The Atrx Chromatin Remodeling Protein, Kristin D. Kernohan
Electronic Thesis and Dissertation Repository
Alpha-thalassemia mental retardation, X-linked (ATRX) is a SWI/SNF-like chromatin remodeling protein, enriched at heterochromatic regions of the genome. Disruption of ATRX in humans causes a neurodevelopmental disorder known as ATR‐X Syndrome, and has been linked to paediatric neuronal cancers, suggesting an important role for ATRX in the regulation of chromatin structure in the developing brain. At the outset of this study direct ATRX target genes had not yet been identified. This thesis identifies imprinted genes as targets of ATRX in the developing brain, and explores the mechanism of ATRX regulation at these sites, using the H19/Igf2 imprinted domain as a …