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ChAHP-mediated Chromatin Remodeling Activity Restricts Transcription Factor Access to chromatin

ABSTRACT: Transcriptional control in eukaryotes relies on the coordinated action of chromatin-based regulatory mechanisms, including control of nucleosome occupancy and chromatin modifications. We previously identified the ChAHP complex – comprising the chromatin remodeler CHD4, transcription factor ADNP, and HP1 proteins – as a site-specific transcriptional regulator and antagonist of CTCF engagement with chromatin. However, the molecular basis of these functions remained unresolved. Here, we show that ChAHP-associated CHD4 is essential for transposon repression, while HP1 proteins are dispensable. We further demonstrate that CHD4’s remodeling activity is not required for chromatin binding, but is critical for both retrotransposon silencing and efficient CTCF antagonism. We propose ADNP is a sequence-specific recruiter of chromatin remodeling activity, facilitating transcriptional control and localized modulation of chromatin architecture.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Stem Cell, Embryonic Stem Cell

SUBMITTER: Jan Seebacher

LAB HEAD: Marc Buehler

PROVIDER: PXD064333 | Pride | 2026-07-17

REPOSITORIES: Pride

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			Action	DRS
	2024-12-02-decoys-MOUSE__230321_contamMQ.fasta.fas	Fasta
	4566_sdrf.tsv	Tabular
	FragPipe_4566_MaxLFQ.intensity_MinProbGlobal_none_limma_einprot0.9.6_public.html	Other
	L3_241201_Vyt_4566_Neg_S01.raw	Raw
	L3_241201_Vyt_4566_Neg_S01_calibrated.mzML	Mzml

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ChAHP-mediated Chromatin Remodeling Activity Restricts Transcription Factor Access to chromatin

Project description:Transcriptional control in eukaryotes relies on the coordinated action of chromatin-based regulatory mechanisms, including control of nucleosome occupancy and chromatin modifications. We previously identified the ChAHP complex – comprising the chromatin remodeler CHD4, transcription factor ADNP, and HP1 proteins – as a site-specific transcriptional regulator and antagonist of CTCF engagement with chromatin. However, the molecular basis of these functions remained unresolved. Here, we show that ChAHP-associated CHD4 is essential for transposon repression, while HP1 proteins are dispensable. We further demonstrate that CHD4’s remodeling activity is not required for chromatin binding, but is critical for both retrotransposon silencing and efficient CTCF antagonism. We propose ADNP is a sequence-specific recruiter of chromatin remodeling activity, facilitating transcriptional control and localized modulation of chromatin architecture.

2026-07-17 | PXD064364 | Pride

ChAHP and ChAHP2 control diverse retrotransposons by complementary activities.

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 HP1-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.

2025-08-05 | PXD048314 | Pride

ChAHP Displaces Transcriptional Regulators Through Active Chromatin Remodeling [RNAseq]

Project description:Transcriptional control in eukaryotes relies on the coordinated action of chromatin-based regulatory mechanisms, including control of nucleosome occupancy and chromatin modifications. We previously identified the ChAHP complex – comprising the chromatin remodeler CHD4, transcription factor ADNP, and HP1 proteins – as a repressor of SINE B2 retrotransposons and site-specific regulator of CTCF engagement with chromatin. However, the molecular basis of these functions remained unresolved. Here, we show that ChAHP-associated CHD4 is essential for SINE B2 repression, while HP1 proteins are dispensable. We further demonstrate that CHD4’s remodeling activity is not required for chromatin binding, but is critical for both retrotransposon silencing and efficient CTCF antagonism. We propose ChAHP is a sequence-specific recruiter of chromatin remodeling activity, facilitating transcriptional control and localized modulation of chromatin architecture.

2025-07-21 | GSE297862 | GEO

ChAHP Displaces Transcriptional Regulators Through Active Chromatin Remodeling [ChIPseq]

Project description:Transcriptional control in eukaryotes relies on the coordinated action of chromatin-based regulatory mechanisms, including control of nucleosome occupancy and chromatin modifications. We previously identified the ChAHP complex – comprising the chromatin remodeler CHD4, transcription factor ADNP, and HP1 proteins – as a repressor of SINE B2 retrotransposons and site-specific regulator of CTCF engagement with chromatin. However, the molecular basis of these functions remained unresolved. Here, we show that ChAHP-associated CHD4 is essential for SINE B2 repression, while HP1 proteins are dispensable. We further demonstrate that CHD4’s remodeling activity is not required for chromatin binding, but is critical for both retrotransposon silencing and efficient CTCF antagonism. We propose ChAHP is a sequence-specific recruiter of chromatin remodeling activity, facilitating transcriptional control and localized modulation of chromatin architecture.

2025-07-21 | GSE297861 | GEO

ChAHP Displaces Transcriptional Regulators Through Active Chromatin Remodeling [gNOMEseq]

Project description:Transcriptional control in eukaryotes relies on the coordinated action of chromatin-based regulatory mechanisms, including control of nucleosome occupancy and chromatin modifications. We previously identified the ChAHP complex – comprising the chromatin remodeler CHD4, transcription factor ADNP, and HP1 proteins – as a repressor of SINE B2 retrotransposons and site-specific regulator of CTCF engagement with chromatin. However, the molecular basis of these functions remained unresolved. Here, we show that ChAHP-associated CHD4 is essential for SINE B2 repression, while HP1 proteins are dispensable. We further demonstrate that CHD4’s remodeling activity is not required for chromatin binding, but is critical for both retrotransposon silencing and efficient CTCF antagonism. We propose ChAHP is a sequence-specific recruiter of chromatin remodeling activity, facilitating transcriptional control and localized modulation of chromatin architecture.

2025-07-21 | GSE297860 | GEO

ChAHP and ChAHP2 control diverse retrotransposons by complementary activities.

2025-08-05 | PXD048310 | Pride

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 (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.

2019-09-05 | GSE125129 | GEO

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

2024-06-25 | GSE253066 | GEO

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