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Epigenetic Mechanisms of Gene Regulation on the X Chromosome in B and T Lymphocytes Natalie E Toothacre
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Toothacre, Natalie E., author.
- Language:
- English
- Subjects (All):
- Molecular biology.
- Genetics.
- Immunology.
- Cellular biology.
- 0307.
- 0369.
- 0982.
- 0379.
- Local Subjects:
- Molecular biology.
- Genetics.
- Immunology.
- Cellular biology.
- 0307.
- 0369.
- 0982.
- 0379.
- Physical Description:
- 1 electronic resource (175 pages)
- Contained In:
- Dissertations Abstracts International 86-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2025
- Language Note:
- English
- Summary:
- X chromosome inactivation (XCI) is an epigenetic mechanism in female mammals where one X chromosome is transcriptionally inactivated through the synergistic action of Xist RNA, heterochromatic marks, and DNA methylation to equalize X-linked gene expression between males and females. XCI is dynamic in female T and B cells, as cytological enrichment of Xist RNA and heterochromatic marks on the inactive X chromosome (Xi) are absent in naive T and B cells yet return following mitogenic stimulation. Here, we find dosage compensation of the Xi in T and B cells with cell-type and state-specific XCI escape genes. We examine the epigenetic modifications associated with transcriptional silencing of the Xi in T and B cells during dynamic XCI, and asked whether Xist RNA or the Xist binding protein hnRNPU is required for heterochromatic mark deposition and retention following B cell stimulation. We find that the Xi in naive T and B cells is depleted for H2AK119Ub but enriched for H3K27me3, which maintains an epigenetic memory of XCI. Upon T or B cell stimulation, H3K27me3 and H2AK119Ub accumulate across the Xi. Additionally, the Xi in B cells is depleted for H3K9me3 but enriched for DNA methylation. Upon B cell stimulation, hnRNPU is required to localize Xist RNA to the Xi, and Xist-independent H3K27me3 and Xist-dependent H2AK119Ub modifications accumulate across the Xi with temporal and spatial specificity. Our findings reveal the importance of Xist RNA, hnRNPU, H3K27me3, H2AK119Ub, and DNA methylation marks for the epigenetic integrity of X-linked genes across the Xi following female T and B cell stimulation
- Notes:
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- Advisors: Anguera, Montserrat C. Committee members: Wu, Hao; Bartolomei, Marisa S.; Jordan, Martha S.; Conine, Colin C.
- Ph.D. University of Pennsylvania 2025
- Local Notes:
- School code: 0175
- ISBN:
- 9798280759336
- Access Restriction:
- Restricted for use by site license
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