Design Principles of Mammalian Transcriptional Regulation / Caroline R. Bartman.

Format:

• Book
• Thesis/Dissertation

Author/Creator:

• Bartman, Caroline R., author.

Contributor:

• Blobel, Gerd A., degree supervisor.
• Raj, Arjun, degree supervisor.
• University of Pennsylvania. Immunology, degree granting institution.

Language:

English

Subjects (All):

• Genetics.
• Immunology.
• Immunology--Penn dissertations.
• Penn dissertations--Immunology.

Local Subjects:

• Genetics.
• Immunology.
• Immunology--Penn dissertations.
• Penn dissertations--Immunology.

Genre:

• Academic theses.

Physical Description:

1 online resource (131 pages)

Contained In:

Dissertations Abstracts International 80-07B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2018.

Language Note:

English

System Details:

• Mode of access: World Wide Web.
• text file

Summary:

Transcriptional regulation occurs via changes to different biochemical steps of transcription, but it remains unclear which steps are subject to change upon biological perturbation. Single cell studies have revealed that transcription occurs in discontinuous bursts, suggesting that features of such bursts like burst fraction (what fraction of time a gene spends transcribing RNA) and burst intensity could be points of transcriptional regulation. Both how such features might be regulated and the prevalence of such modes of regulation are unclear. I first used a synthetic transcription factor to increase enhancer-promoter contact at the β-globin locus. Increasing promoter-enhancer contact specifically modulated the burst fraction of β-globin in both immortalized mouse and primary human erythroid cells. This finding raised the question of how generally important the phenomenon of burst fraction regulation might be, compared to other modes of regulation. For example, biochemical studies have suggested that stimuli predominantly affect the rate of RNA polymerase II (Pol II) binding and the rate of Pol II release from promoter-proximal pausing, but the prevalence of these modes of regulation compared to changes in bursting had not been examined. I combined Pol II ChIP-seq and single cell transcriptional measurements to reveal that an independently regulated burst initiation step is required before polymerase binding can occur, and that the change in burst fraction produced by increased enhancer-promoter contact was caused by an increased burst initiation rate. Using a number of global and targeted transcriptional regulatory perturbations, I showed that biological perturbations regulated both burst initiation and polymerase pause release rates, but seemed not to regulate polymerase binding rate. Our results suggest that transcriptional regulation primarily acts by changing the rates of burst initiation and polymerase pause release.

Notes:

• Source: Dissertations Abstracts International, Volume: 80-07, Section: B.
• Publisher info.: Dissertation/Thesis.
• Advisors: Blobel, Gerd A.; Raj, Arjun; Committee members: Marisa Bartolomei; Craig Bassing; Warren Pear.
• Department: Immunology.
• Ph.D. University of Pennsylvania 2018.

Local Notes:

School code: 0175

ISBN:

9780438767225

Access Restriction:

• Restricted for use by site license.
• This item must not be sold to any third party vendors.