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Series GSE255357 Query DataSets for GSE255357
Status Public on Feb 03, 2025
Title Pharmacological Modulation of BMAL1 Alters Circadian Dynamics and the Macrophage Immune Response
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The master transcription factor BMAL1-CLOCK is crucial for orchestrating rhythmic gene expression and governing circadian rhythms. Pharmacological manipulation of this central circadian regulator requires accessible protein cavities and selective compounds. By targeting BMAL1 through a resident cavity in its PAS-B domain, we demonstrate that the small-molecule Core Circadian Modulator (CCM) penetrates and substantially expands this pocket. Biochemical and cellular analyses validate CCM's target engagement selectivity, enabling direct access to BMAL1's transcriptional activities. CCM induces dose-dependent changes in PER2-Luc macrophage oscillations and selectively modifies expression patterns of circadian controlled genes. In activated macrophages, CCM modulates BMAL1-CLOCK controlled inflammatory and phagocytic pathways to promote their downregulation. Our findings demonstrate the feasibility of directly targeting BMAL1-CLOCK as a strategy for circadian regulation and targeting circadian-regulated processes
 
Overall design To investigate the specificity and effects of pharmacological manipulation of Bmal1, bone-marrow derived macrophages from both myeloid cell specific Bmal1-KO mice and littermate controls were treated with CCM. The effect of inflammation was monitored: this was done under both basal and stimulated conditions.
 
Contributor(s) Bailey L, Ray D
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Submission date Feb 08, 2024
Last update date Feb 03, 2025
Contact name Laura Bailey
E-mail(s) laura.bailey@exeter.ox.ac.uk
Organization name University of Oxford
Department Oxford Centre for Diabetes, Endocrinology and Metabolism
Street address Radcliffe Department of Medicine
City Oxford
ZIP/Postal code OX3 7LE
Country United Kingdom
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (36)
GSM8070291 BMDM, Bmal1-KO, LPS, rep1
GSM8070292 BMDM, Bmal1-KO, CCM, rep1
GSM8070293 BMDM, Bmal1-KO, LPS + CCM, rep1
Relations
BioProject PRJNA1074737

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE255357_gene_count.txt.gz 3.0 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA

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