Sculpting 3D chromatin folding via genome editing / Di Zhang.

Format:

Book

Thesis/Dissertation

Author/Creator:

Zhang, Di, author.

Contributor:

Blobel, Gerd A., degree supervisor.

Bartolomei, Marisa S., degree supervisor.

University of Pennsylvania. Department of Genomics and Computational Biology, degree granting institution.

Language:

English

Subjects (All):

Genetics.

Biology.

Biophysics.

Genomics and computational biology--Penn dissertations.

Penn dissertations--Genomics and computational biology.

Local Subjects:

Genetics.

Biology.

Biophysics.

Genomics and computational biology--Penn dissertations.

Penn dissertations--Genomics and computational biology.

Genre:

Academic theses.

Physical Description:

1 online resource (120 pages)

Contained In:

Dissertations Abstracts International 82-07B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2020.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

Animal chromosomes are partitioned into contact domains. Pathogenic domain disruptions can result from chromosomal rearrangements or perturbation of architectural factors. However, such broad-scale alterations are insufficient to define the minimal requirements for domain formation. Moreover, to what extent domains can be engineered is only beginning to be explored. In an attempt to create contact domains, we inserted a 2-kb DNA sequence underlying a tissue-invariant domain boundary-containing a CTCF binding site (CBS) and a transcription start site (TSS)-into 16 ectopic loci across 11 chromosomes, and characterized its architectural impact. Depending on local constraints, this fragment variably formed new domains, partitioned existing ones, altered compartmentalization, and initiated contacts reflective of chromatin loop extrusion. Deletions of the CBS or the TSS individually or in combination within inserts revealed their distinct contributions to genome folding. Altogether, short DNA insertions can suffice to shape the spatial genome in a manner influenced by chromatin context. Additionally, we frame our findings in the context of recent advances in experimentally creating chromatin loops, contact domains, boundaries, and compartments. Furthermore, we explore parallels between this emerging theme and natural evolution of mammalian genomes with increasing architectural complexity. Finally, we provide a perspective on how insights arising from recent gain-of-function studies may inform future endeavors towards engineering the three-dimensional (3D) genome.

Notes:

Source: Dissertations Abstracts International, Volume: 82-07, Section: B.

Advisors: Blobel, Gerd A.; Bartolomei, Marisa S.; Committee members: Mitchell Lazar; Arjun Raj; Feng Yue.

Department: Genomics and Computational Biology.

Ph.D. University of Pennsylvania 2020.

Local Notes:

School code: 0175

ISBN:

9798557052535

Access Restriction:

Restricted for use by site license.

This item is not available from ProQuest Dissertations & Theses.

This item must not be sold to any third party vendors.