Dissecting enhancer-promoter specificity in mammalian development
Active Project Grant Awarded Last action
- Award ID
- F31HD122363
- Recipient
-
University Of California Irvine UEI MJC5FCYQTPE6
- Awarding agency
-
National Institute of Child Health and Human Development
National Institutes of Health, Department of Health and Human Services
- Obligated
- $87,844
Award facts
- Assistance listing
- 93.865 Child Health and Human Development Extramural Research
- Completion date 0% complete
- Originally
- Place of performance
- Irvine, CA 92697, USA
Award details come from USAspending.gov.
Description
- Abstract
- Enhancers are short noncoding DNA sequences with cell-type specific activity that regulate the activation of genes during development. Enhancers are known to contact the promoter of their target gene when active, but exactly how enhancers recognize their precise target is unclear. Some enhancers are genomic neighbors to their target gene, but others act over long distances and can bypass or "skip" more proximal gene promoters. However, there are few verified developmental enhancers with known target genes, making IT challenging to assess the epigenetic factors that provide enhancer-promoter specificity and enable promoter skipping. Existing work to address this question is hindered by technical limitations that prevent efficient identification of enhancers, understanding their cell-type specific activity, and the annotation of their genome-wide interactions. To address this, I have developed a comparative bioinformatic pipeline that interrogates possible epigenetic markers of enhancer activity and generated preliminary evidence showing my ability to create high resolution chromatin contact maps in pure cell populations. The objective of this proposal is to identify a predictive signature of active enhancers (aim 1) and characterize the interactions of thousands of developmental enhancers at nucleosome resolution (aim 2). To accomplish aim 1, I will analyze traditional and novel epigenetic markers for enhancers to determine which most effectively detects cell-type specific activity of characterized enhancers. I will then test this metric's ability to predict active enhancers by testing uncharacterized regions using in vivo reporters. To achieve aim 2, I will perform enhancer capture-micro-C against known and predicted enhancers in pure cell populations for four key embryonic lineages, to map enhancers to their target genes. The proposed research will provide valuable genome-wide insight into our understanding of how frequently developmental enhancers skip proximal promoters to regulate their target gene and allow cell-type specific assessment of the epigenetic factors that contribute to this specificity. During the fellowship period, DR. Evgeny kvon will serve as my sponsor, providing expertise in gene regulation, developmental biology, and mouse genome engineering. With his support and input, I have designed a thorough training plan that will promote my development as an independent researcher and biology educator. Under this proposal, I will learn new skills in mouse transgenics, epigenetic techniques, and developmental biology. My professional development is supported by training in scientific communication, curriculum development, and mentorship.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $43,922 | |
| Amendment | $0 | |
| Original award | $43,922 |
Quick answers
Who received award F31HD122363?
F31HD122363 was awarded to University Of California Irvine by National Institute of Child Health and Human Development (National Institutes of Health) on December 1, 2026.
How much is award F31HD122363 worth?
$87,844 has been obligated on F31HD122363.
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