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ChAHP and ChAHP2 control diverse retrotransposons by complementary activities [ChIP-seq]

ABSTRACT: Retrotransposon control in mammals is an intricate process that is effectuated by a broad network of chromatin regulatory pathways. We previously discovered ChAHP, a protein complex with repressive activity against SINE retrotransposons, composed of the transcription factor ADNP, chromatin remodeler CHD4, and HP1 proteins. Here we identify ChAHP2, a protein complex homologous to ChAHP, wherein ADNP is replaced by ADNP2. ChAHP2 is predominantly targeted to ERVs and LINEs, via HP1b-mediated binding of H3K9 trimethylated histones. We further demonstrate that ChAHP also binds these elements in a mechanistically equivalent manner to ChAHP2, and distinct from DNA sequence-specific recruitment at SINEs. Genetic ablation of ADNP2 alleviates ERV and LINE1 repression, which is synthetically exacerbated by additional depletion of ADNP. Together, our results reveal that the ChAHP and ChAHP2 complexes function to control both non-autonomous and autonomous retrotransposons by complementary activities, further adding to the complexity of mammalian transposon control.

ORGANISM(S): Mus musculus

PROVIDER: GSE253066 | GEO | 2024/06/25

REPOSITORIES: GEO

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ChAHP and ChAHP2 control diverse retrotransposons by complementary activities [RNA-seq]

Project description:Retrotransposon control in mammals is an intricate process that is effectuated by a broad network of chromatin regulatory pathways. We previously discovered ChAHP, a protein complex with repressive activity against SINE retrotransposons, composed of the transcription factor ADNP, chromatin remodeler CHD4, and HP1 proteins. Here we identify ChAHP2, a protein complex homologous to ChAHP, wherein ADNP is replaced by ADNP2. ChAHP2 is predominantly targeted to ERVs and LINEs, via HP1b-mediated binding of H3K9 trimethylated histones. We further demonstrate that ChAHP also binds these elements in a mechanistically equivalent manner to ChAHP2, and distinct from DNA sequence-specific recruitment at SINEs. Genetic ablation of ADNP2 alleviates ERV and LINE1 repression, which is synthetically exacerbated by additional depletion of ADNP. Together, our results reveal that the ChAHP and ChAHP2 complexes function to control both non-autonomous and autonomous retrotransposons by complementary activities, further adding to the complexity of mammalian transposon control.

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ChAHP and ChAHP2 control diverse retrotransposons by complementary activities [ATAC-seq]

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ChAHP (Adnp, Chd4, HP1) mediates sequence-specific recruitment of HP1 independent of H3K9 methylation

Project description:Activity-dependent neuroprotective protein (ADNP) is one of the most frequent autism spectrum disorder-associated gene products known to date. Here we show that Adnp interacts with the chromatin remodeler Chd4 and the heterochromatin protein HP1 to form a stable complex, which we refer to as ChAHP. Genetic ablation of ChAHP components or DNA binding sites in embryonic stem cells prematurely activates lineage-specific genes, revealing an important role for Adnp in restraining the differentiation capacity of pluripotent cells. Adnp targets the ChAHP complex to specific sequence motifs at euchromatic loci, representing an H3K9 methylation-independent mechanism of HP1 recruitment and gene silencing.

2018-05-23 | GSE97945 | GEO

The ChAHP complex counteracts chromatin looping at Ctcf sites that have emerged from recent SINE expansions

Project description:Ctcf and cohesin are key players in the three dimensional organization of chromatin. Whereas genome-wide Ctcf binding has diverged substantially between species due to transposon-mediated motif expansions, demarcation of topologically associating domains (TADs) by Ctcf is remarkably well conserved. Yet, the Ctcf consensus motif poorly predicts TADs and the majority of Ctcf sites are not at TAD boundaries. Here we demonstrate that the ChAHP complex (Chd4, Adnp, HP1) competes with Ctcf for a common set of genomic binding sites. In absence of ChAHP, novel insulated regions are formed at ChAHP bound sites, whereas proximal canonical boundaries are weakened. These data reveal that Ctcf-mediated loop formation is modulated by a distinct zinc-finger protein complex. Strikingly, ChAHP bound loci are mainly situated within evolutionary young SINE B2 transposable elements. This further implicates ChAHP in maintenance of evolutionary conserved spatial chromatin organization by buffering novel Ctcf binding sites that emerged through SINE expansions.

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The HP1 protein interactome of mouse embryonic stem cells

Project description:The family of Heterochromatin Protein 1 (HP1) consists of highly conserved proteins, which have important functions in the nucleus of eukaryotic cells. In mammals there are three HP1 paralogs: HP1(alpha), Hp1(beta), and Hp1(gamma)They are encoded by the Cbx5, Cbx1, and Cbx3 genes, respectively. Hp1 and Hp1 stably interact with Chd4 and Adnp to form the ChAHP complex. In this project, Chd4, Adnp, and the three Cbx genes were endogenously tagged with a FLAG-Avi tag in mouse embryonic stem cells. The tagged proteins were subjected to tandem-affinity purification and analysis by mass spectrometry.

2018-05-22 | PXD006226 | Pride

ChAHP and ChAHP2 control diverse retrotransposons by complementary activities

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-25 | GSE253069 | GEO

Genome-wide analysis of Gtf3c1, RNAP3 occupancy and H3K4me1, H3K27ac chromatin modifications in primary mouse cortical neurons

Project description:SINEs are a highly abundant class of retrotransposons that were initially considered a non-functional “junk” DNA due to their non coding, repetitive nature. SINEs frequently possess an internal RNAPIII promoter, which recruits the RNAPIII transcriptional machinery, including the general nuclear complex TFIIIC. We recently discovered that in response to neuronal depolarisation, SINEs may represent a novel class of neuronal enhancers and reasoned that RNAPIII and TFIIIC binding may provide a means of identifying enhancer SINEs genome-wide. To this end, we first performed ChIPseq analysis on resting and depolarised mouse cortical neurons, using an antibody that targets the DNA binding subunit of TFIIIC (Gtf3c1), RNA Polymerase III and the enhancer markers H3K4me1 and H3K27ac .

2017-12-05 | GSE75191 | GEO

Transcription profiling of mouse ADNP knockout vs wild type

Project description:The putative transcription factor, activity-dependent neuroprotective protein (ADNP) is a zinc finger and homeodomain - like profile containing protein. ADNP knockout mice die at day 9 of gestation. To reveal ADNP-associated pathways, a 22,690- Affymetrix probe array was used on ADNP knockout and control embryos. References:; Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. J Neurochem. 1999 Mar;72(3):1283-93. PMID: 10037502 [PubMed - indexed for MEDLINE]; Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem. 2001 Jan 5;276(1):708-14. PMID: 11013255 [PubMed - indexed for MEDLINE]; Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res Dev Brain Res. 2003 Aug 12;144(1):83-90. PMID: 12888219 [PubMed - indexed for MEDLINE] Experiment Overall Design: To identify downstream target genes of ADNP, we examined global gene expression profiles of whole E9 knockout embryos (KO - ADNP -l-), their wild-type (WT - ADNP +l+ ) and their heterozygous (H - ADNP âl+ ) littermates, using the Affymetrix Murine Genome 430A oligonucleotide microarrays. Gestation day 9 was chosen as it is the period at which embryos lacking ADNP exhibit distinct morphological and developmental changes prior to degeneration and in uterus absorption. Total RNA was extracted from four ADNP knockout embryos, four normal embryos and six heterozygous embryos. A pool of two genotype identical littermates was used on seven different arrays (pooling of two embryos was necessary to obtain enough RNA on each of the gene microarrays).

2008-06-12 | E-GEOD-4068 | biostudies-arrayexpress

Mus musculus

Project description:ChAHP (Adnp, Chd4, HP1) mediates sequence-specific recruitment of HP1 independent of H3K9 methylation

| PRJNA383413 | ENA

RNA-seq of the U2OS cell line (Human Bone Osteosarcoma Epithelial Cells) treated with ZMYM2, TRIM28 or ADNP knock down against the control conditions.

Project description:In order to investigate the functions of the zinc finger transcription regulator ZMYM2 and the different types of ZMYM2 binding complex with TRIM28 or ADNP, we generated the RNA-seq data with ZMYM2, TRIM28 or ADNP siRNA in U2OS cells and the control cases with siNT in U2OS cells as well.

2023-06-01 | E-MTAB-12291 | biostudies-arrayexpress

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