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Sub-nuclear transcription factor targeting remodels heterochromatin to activate compartmentalized gene programs [RNA-Seq]

ABSTRACT: Sub-nuclear transcription factor targeting remodels heterochromatin to activate compartmentalized gene programs [RNA-Seq]

PROVIDER: PRJNA1168539 | ENA |

REPOSITORIES: ENA

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HAND2 invades nucleolar condensates to pioneer lineage-specific cardiac pacemaker gene programs [ATAC, Cut & Tag]

Project description:HAND2 invades nucleolar condensates to pioneer lineage-specific cardiac pacemaker gene programs [ATAC, Cut & Tag]

| PRJNA1273088 | ENA

HAND2 invades nucleolar condensates to pioneer lineage-specific cardiac pacemaker gene programs [RNA-Seq]

Project description:Sub-nuclear localization of heterochromatin enables stable lineage-specific gene repression. The mechanisms by which pioneer transcription factors (TFs) access these loci to selectively activate lineage-specific genes remain poorly understood. Here, using a model of TF-induced cardiac reprogramming, we show that Hand2’s ability to reprogram cells requires its selective compartmentalization within perinucleolar heterochromatin wherein many key target genes reside. We identify the nucleolar targeting region of Hand2, which is mechanistically separable from DNA-binding. Using a series of separation of function mutants, we find that compartmentalization creates high local concentrations of Hand2 homodimers required for binding of suboptimal DNA motifs within lineage-specific gene enhancers. Altogether, our results establish a causal relationship between TF sub-nuclear localization and selective activation of lineage-specific gene programs. Thus, our data support the notion that lineage-specific programs are functionally compartmentalized within the nucleus, and we provide a mechanistic model by which TF sub-nuclear localization orchestrates selective activation of lineage specific genes.

2025-08-05 | GSE278736 | GEO

HAND2 invades nucleolar condensates to pioneer lineage-specific cardiac pacemaker gene programs [ATAC, Cut & Tag]

2025-08-05 | GSE299217 | GEO

Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (RNA-seq)

Project description:Gata4, Mef2c, Hand2, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here we explored the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and endogenous sinoatrial node (SAN), yet key regulatory networks remain missing. We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression. Moreover, we identify a novel Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N-terminus. By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation. Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.

2019-07-30 | GSE124337 | GEO

Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (ATAC-seq)

2019-07-30 | GSE124336 | GEO

Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming

Project description:Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming

| PRJNA511667 | ENA

Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (RNA-seq)

Project description:Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (RNA-seq)

| PRJNA511670 | ENA

Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (ATAC-seq)

Project description:Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (ATAC-seq)

| PRJNA511669 | ENA

Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair

Project description:We investigated the role of the nucleolar protein Treacle in organizing and regulating the nucleolus in human cells. Our results support Treacle’s ability to form liquid-like phase condensates through electrostatic interactions among molecules. The formation of these biomolecular condensates is crucial for segregating nucleolar fibrillar centers from the dense fibrillar component and ensuring high levels of rRNA gene transcription and accurate rRNA processing. Both the central and C-terminal domains of Treacle are required to form liquid-like condensates. The initiation of phase separation is attributed to the C-terminal domain. The central domain is characterized by repeated stretches of alternatively charged amino-acid residues and is vital for condensate stability. Overexpression of mutant forms of Treacle that cannot form liquid-like phase condensates compromises the assembly of fibrillar centers, suppressing rRNA gene transcription and disrupting rRNA processing. These mutant forms also fail to recruit DNA topoisomerase II binding protein 1 (TOPBP1), suppressing the DNA damage response in the nucleolus.

2025-03-26 | GSE292850 | GEO

HAND2 regulates regional chromation modification [HAND2-knockdown_histone_ChIPseq]

Project description:HAND2 regulates regional chromation modification [HAND2-knockdown_histone_ChIPseq]

| PRJNA762918 | ENA