NLM IRP Seminar Schedule
UPCOMING SEMINARS
RECENT SEMINARS
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July 23, 2024 Yu group
Yu Group Research Update -
July 18, 2024 Xiaofang Jiang
Jiang Lab research updates -
May 30, 2024 Deepak Gupta
Towards Answering Health-related Questions from Medical Videos: Datasets and Approaches -
May 28, 2024 Harutyun Saakyan
Simulation of protein fold evolution with atomistic details -
May 23, 2024 Leslie Ronish
Identification of fold-switching proteins by FLIM-FRET
Scheduled Seminars on April 16, 2024
Contact NLM_IRP_Seminar_Scheduling@mail.nih.gov with questions about this seminar.
Abstract:
Evolutionary turnover in the cis-regulatory elements (CREs) of the human genome accounts for more than 90% of the phenotypic and disease associated traits. Some CREs undergo higher rates of substitution and if mutated, may be more likely to result in phenotypic changes. Genomic substrates of novel enhancer activity can be repurposed CREs, transposable elements, or neutral sequences leading to de-novo emergence. We used a deep learning model that’s capable of correlating nucleotide changes to differential enhancer activity and found that a large majority of CREs between humans and our next closest relatives, chimpanzees, have evolved by repurposing regulatory activity from other cell types. Our results highlight a set of predisposed elements that are more suited to regulatory innovation due to their sequence composition of transcription factor binding sites (TFBSs). TFBS enrichment analysis suggests that the repurposed elements do not conform to specific transcription programs. I will discuss results of our analysis that leads us to hypothesize that the repurposed CREs may act as redundant enhancers, are inefficiently integrated into the transcriptional circuitry, and buffer the impact of unfavorable mutations to confer regulatory robustness.