Asset Details
Do you wish to reserve the book?
Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells
Do you wish to request the book?
Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells
2024
Overview
Cis
-regulatory elements (CREs) interact with
trans
regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of the adjacent costimulatory genes
CD28
,
CTLA4
and
ICOS
, encoding regulators of T cell-mediated immunity. Tiling CRISPR interference (CRISPRi) screens in primary human T cells, both conventional and regulatory subsets, uncovered gene-, cell subset- and stimulation-specific CREs. Integration with CRISPR knockout screens and assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling identified
trans
regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. We then discovered a critical CCCTC-binding factor (CTCF) boundary that reinforces CRE interaction with
CTLA4
while also preventing promiscuous activation of
CD28
. By systematically mapping CREs and associated
trans
regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.
Functional characterization of the regulatory landscape of the adjacent costimulatory genes
CD28
,
CTLA4
and
ICOS
in primary human T cell subsets identifies context-dependent programs controlling this locus critical for immune homeostasis.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Biomedical and Life Sciences
/ CCCTC-Binding Factor - genetics
/ CCCTC-Binding Factor - metabolism
/ CIS gene
/ CRISPR
/ Decoding
/ Genomics
/ Humans
/ Inducible T-Cell Co-Stimulator Protein - genetics
/ Inducible T-Cell Co-Stimulator Protein - metabolism
/ Proteins
/ Tiling
