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Series GSE236182 Query DataSets for GSE236182
Status Public on Dec 04, 2023
Title Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Although Kdm1a is the most expressed histone demethylase in neurons, its molecular function in the adult brain remains unknown. Here, we found that inducible and forebrain-restricted knockout (ifKO) mice, in which Kdm1a is specifically eliminated in forebrain excitatory neurons during adulthood, display a prominent transcriptional and epigenomic dysregulation signature characterized by the neuronal expression of nonneuronal genes. The combination of super-resolution microscopy images and multi-omic analysis integrating transcriptome, epigenome and chromatin conformation data showed that these genes are target of the polycomb repressor complex 2 (PRC2) and locate in H3K27me3-microdomains encapsulated within the euchromatin compartment. Furthermore, functional assays revealed that both the catalytic activity and the N-terminus intrinsically disordered region of Kdm1a, which provides phase separation properties, are needed to maintain the boundaries between these silent micro-domains and the active chromatin environment. As a result, Kdm1a loss led to the spreading of active histone modifications into the PRC2-repressed genes causing their de-repression. Intriguingly, the investigation of aged mice suggested that these boundaries may also weaken during natural aging. Overall, these results underscore the role of Kdm1a safeguarding chromatin compartmentalization, nuclear phase separation and gene silencing in the adult and aging brain.
Overall design Expression profiling, Genome binding/occupancy profiling, and chromosome conformation capture by high throughput sequencing for WT and ifKO-Kdm1a mice. Chromatin interaction analysis with paired-end tag sequencing for CTCF in WT.
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Contributor(s) Niñerola S, del Blanco B, Barco A
Citation(s) 38453932
Submission date Jun 29, 2023
Last update date Mar 08, 2024
Contact name Sergio Niñerola
Phone +34646912958
Organization name CSIC-Instituto de Neurociencias de Alicante
Department Molecular Neurobiology and Neuropathology
Lab Transcriptional and epigenetic mechanisms of neuronal plasticity
Street address Avenida Santiago Ramon y Cajal, s/n
City San Juan de Alicante
State/province Alicante
ZIP/Postal code 03550
Country Spain
Platforms (3)
GPL16417 Illumina MiSeq (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (37)
GSM7519409 RNA_WT, rep1
GSM7519410 RNA_WT, rep2
GSM7519411 RNA_WT, rep3
BioProject PRJNA989189

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Supplementary file Size Download File type/resource 341.4 Mb (ftp)(http) BW 59.8 Mb (ftp)(http) BW 62.2 Mb (ftp)(http) BW
GSE236182_RAW.tar 1.9 Gb (http)(custom) TAR (of BEDGRAPH, BEDPE, BIGWIG, HIC, WIG) 511.6 Mb (ftp)(http) BW 386.8 Mb (ftp)(http) BW 384.0 Mb (ftp)(http) BW 308.2 Mb (ftp)(http) BW 536.6 Mb (ftp)(http) BW 444.6 Mb (ftp)(http) BW 539.3 Mb (ftp)(http) BW 439.4 Mb (ftp)(http) BW
GSE236182_raw_counts.txt.gz 371.8 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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