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Series GSE205232 Query DataSets for GSE205232
Status Public on Dec 13, 2022
Title Loss of the Ash2l subunit of histone H3K4 methyltransferase complexes promotes chromatin compaction at promoters [ChIP-seq H3K4me1,me3]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cell fate decisions are closely associated with changes in gene expression programs. A large number of post-translational modifications of core histones contribute to controlling the expression of genes. A modification that is closely correlated with open chromatin and gene transcription is methylation of lysine 4 of histone H3 (H3K4). It is catalyzed by methyltransferases of the KMT2 family, which require interaction with 4 core subunits, WDR5, RBBP5, ASH2L and DPY30, for catalytic activity. Ash2l is required for organismal development and for tissue homeostasis in the mouse. In mouse embryo fibroblasts (MEFs), the loss of Ash2l results in downregulated gene expression, which provokes a senescence phenotype. We now find that both H3K4 mono- and tri-methylation (H3K4me1 and me3, respectively) are deregulated. H3K4me3 is lost while H3K4me1 is increased at promoters upon knockout of Ash2l. In particular, loss of H3K4me3 at promoters correlates with downregulation of gene expression, which is particularly obvious at CpG island promoters. Ash2l loss results in an increase of histone H3 loading at promoters, paralleled by enhanced chromatin compaction. This is accompanied by an increase of repressing and a decrease of activating histone marks. One of the sequence-specific transcription factors with altered binding upon depletion of Ash2l is CTCF. It is lost from some promoter-associated sites, but gained binding in other regions of the genome. This suggests that in addition to the well-known effects on H3K4 methylation upon depleting KMT2 complex components, Ash2l loss affects chromatin compaction. Whether the decrease of H3K4me3 promotes chromatin compaction at promoters or whether these are independent consequences of Ash2l loss remains to be determined. We suggest that both contribute mechanistically to gene repression and thus to the observed cellular effects.
Overall design Two independently generated mouse embryo fibroblast lines (from two different litters) with floxed exon 4 of Ash2l (KO1 and KO2). Two additional lines with wt Ash2l (WT1 and WT2). All express Cre-ER and were immortalized using shArf. Cells were treated -/+ 4-hydroxytamoxifen for 5 days.ChIP was performed with antibodies for H3K4me1 and H3K4me3.
Contributor(s) Barsoum M, Stenzel AT, Bochyńska A, Kuo C, Tsompanidis A, Sayadi Boroujeni R, Bussmann P, Lüscher-Firzlaff J, Costa IG, Lüscher B
Citation(s) 36513698
Submission date May 31, 2022
Last update date Jan 05, 2023
Contact name Mirna Barsoum
Phone 00492418088915
Organization name Uniklinik RWTH Aachen
Department Institute of Biochemistry and Molecular Biology
Lab Bernhard Lüscher
Street address Pauwelsstrasse 30
City Aachen
State/province North Rhine Westphalia
ZIP/Postal code 52074
Country Germany
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (20)
GSM6208881 ChIPSeq_H3K4me1_iMEF1_input
GSM6208882 ChIPSeq_H3K4me1_iMEF1_WT_HOT_plus
GSM6208883 ChIPSeq_H3K4me1_iMEF1_WT_HOT_minus
This SubSeries is part of SuperSeries:
GSE205233 Loss of the Ash2l subunit of histone H3K4 methyltransferase complexes promotes chromatin compaction at promoters.
BioProject PRJNA844127

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Supplementary file Size Download File type/resource
GSE205232_RAW.tar 3.6 Gb (http)(custom) TAR (of BW)
GSE205232_Table_S1_ChIP-seq_H3K3me1_H3K4me3_KO1_KO2.xls.gz 15.9 Mb (ftp)(http) XLS
GSE205232_Table_S2_ChIP-seq_H3K4me_TF_enrichment.xlsx 67.0 Kb (ftp)(http) XLSX
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