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

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

PROVIDER: PRJNA511667 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8368600_1.fastq.gz	Fastqsanger.gz
	SRR8368600_2.fastq.gz	Fastqsanger.gz
	SRR8368610_1.fastq.gz	Fastqsanger.gz
	SRR8368610_2.fastq.gz	Fastqsanger.gz
	SRR8368601_1.fastq.gz	Fastqsanger.gz

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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

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 (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:Gata4, Hand2, Mef2c, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here, we explore 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 the 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 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.

| S-EPMC6657359 | biostudies-literature

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

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

2019-07-30 | GSE124338 | GEO

Gene profiling of Hand2 target genes and transcriptional regulation of Hand2 expression in the postnatal myocardium

Project description:In humans, cardiac hypertrophy is the principal risk factor for the development of overt heart failure and sudden cardiac death from lethal arrhythmias. Although aberrant reactivation of fetal² gene programs is intricately linked to maladaptive hypertrophy of postnatal cardiomyocytes, loss of cardiac function and heart failure, the transcription factors driving these gene programs remain ill defined. We report that the basic helix-loop-helix (bHLH) transcription factor dHAND/Hand2 is re-expressed in the mammalian postnatal myocardium in response to stress signaling. Interestingly, mutant mice overexpressing Hand2 in otherwise healthy ventricular myocytes developed a phenotype of pathological hypertrophy. In contrast, conditional gene-targeted Hand2 mice demonstrated a marked resistance to pressure overload-induced hypertrophy, fibrosis, ventricular dysfunction and induction of a fetal gene program. These data suggest a critical role for the Hand2 transcription factor during hypertrophic remodeling and heart failure. To gain more mechanistically insight in the processes underlying heart failure, we here identified Hand2 target genes by microarray gene expression profiling. RNA samples were collected 4 weeks after sham or TAC surgery (to induce pressure overload) of both tamoxifen-treated Hand2f/f (WT) and MCM-Hand2f/f (KO) mice.

2013-11-15 | E-MTAB-1821 | biostudies-arrayexpress

HAND2 regulates regional chromation modification [HAND2-knockdown_histone_ChIPseq]

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

| PRJNA762918 | ENA

Gene expression profiling of uterine stromal cells isolated from Hand2 floxed and Hand2 ablated mice on day 4 of pregnancy

Project description:Our previous study revealed that the basic helix-loop-helix transcription factor Hand2 is a downstream target of progesterone signaling in mouse uterine stroma at the time of implantation. Further, conditional deletion of Hand2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity. To identify the downstream targets of Hand2 in the uterus, we performed gene expression profling of uterine stromal cells isolated from Hand2-null mice and the corresponding controls on day4 of pregnancy (the time of implantation). The microarray results revealed elevated expression of mRNAs corresponding to several members of the fibroblast growth factor family in uterine stroma of Hand2-ablated mice. These factors act as paracrine mediators of mitogenic effects of estrogen on the epithleium. Thus, Hand2 is a critical regulator of the uteirne stromal-epithelial communication that directs proper steroid regulation conducive for establshment of pregnancy. We performed conditional ablation of Hand2 in the mouse uterus using the PRcre mouse model. As Hand2 expression is restricted to stromal comaprtment, we isolated uterine stromal cells from day4 pregnant mice (n=5 for each genotype), purified total RNA from these cells, pooled these samples and then hybridized to high density affymetrix microarrays. Control vs. KO.

2011-06-03 | E-GEOD-25881 | biostudies-arrayexpress

Expression data from Hand2 mutant mouse embryos

Project description:Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. Hand2 is involved in coordinating the developmental network of mandibles and the oral apparatus through Hand2-downstream genes and is therefore a major determinant of jaw identity. We used microarrays to detail the global programme of gene expression involved in mandible specification and identified distinct classes of up-regulated genes during this process. Wild-type and Hand2 mutant (Hand2 CAT/+; Wnt1-Cre) embryos were collected at Embryonic day (E) 11.5 or E12.5 for RNA extraction and hybridization on Affymetrix microarrays.

2015-12-15 | E-GEOD-75805 | biostudies-arrayexpress

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