Chromatin loops spanning tens to hundreds of kilobases link promoter-distal regulatory elements such as enhancers to the promoters of their target genes. Many of these loops are cell-type specific and are thought to play a critical role in transcriptional control during cellular differentiation and human development. Recent progress in our ability to detect these loops has significantly advanced our knowledge regarding the molecular components of DNA loops; however, the mechanisms and functions of changes in DNA looping during cellular differentiation remain poorly understood. The goals of our research are to identify the mechanisms through which cells establish new loops during cellular differentiation and to determine how the resulting structures contribute to altered transcriptional output. We will accomplish these goals by: (1) mapping loops, regulatory events, and gene transcription with temporal resolution during cellular differentiation, (2) developing and applying new software to identify and visualize dynamic looping events, and (3) performing targeted mechanistic investigations of loops formed during differentiation. The results of this research will determine both the scope and general principles of DNA loop formation during differentiation, provide new tools for the gene regulation community, and illuminate the functions of the non-coding human genome.

Public Health Relevance

The overarching mission of our research is to understand the mechanisms and functions of DNA loop-based transcriptional regulation during cellular differentiation. We will accomplish this goal by combining existing genomic, bioinformatic, and genome editing technologies with the development of new computational and wet lab tools to interrogate 3D chromatin architecture.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM128645-02
Application #
9747947
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Gaillard, Shawn R
Project Start
2018-07-19
Project End
2023-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Physiology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599