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Epigenetic silencing of HAND2 is a crucial step in endometrial carcinogenesis

ABSTRACT: Here we demonstrate that epigenetic silencing of HAND2 is a key step in endometrial carcinogenesis. We performed an epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancers and controls and identified methylation of HAND2 as one of the most common hypermethylated and silenced genes in endometrial cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE40032 | GEO | 2015/08/15

SECONDARY ACCESSION(S): PRJNA172423

REPOSITORIES: GEO

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Epigenome analysis of endometrium tissue from women with metastatic endometrial cancer.

Project description:The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in endometrium tissues from women with metastatic endometrial cancer. Endometrium tissue samples were drawn from 18 metastatic endometrial cancers. The metastatic endometrial cancer tissue samples were from women (mean age 67.1) who were diagnosed with metastatic endometrial cancer.

2012-02-20 | GSE33422 | GEO

Epigenome analysis of endometrium tissue from women with metastatic endometrial cancer.

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HAND2 regulates regional chromation modification [HAND2-knockdown_histone_ChIPseq]

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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

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.

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Transcription profile of zebrafish hand2 (hanS6 allele) mutant embryos at 19hpf

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Project description:The knockdown of HAND2 affects the regional chromation modification.

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Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma

Project description:The mesothelium forms epithelial membranes that line the bodies cavities and surround the internal organs. Mesothelia widely contribute to organ homeostasis and regeneration, and their dysregulation can result in congenital anomalies of the viscera, ventral wall defects, and mesothelioma tumors. Nonetheless, the embryonic ontogeny and developmental regulation of mesothelium formation has remained uncharted. Here, we combine genetic lineage tracing, in toto live imaging, and single-cell transcriptomics in zebrafish to track mesothelial progenitor origins from the lateral plate mesoderm (LPM). Our single-cell analysis uncovers a post-gastrulation gene expression signature centered on hand2 that delineates distinct progenitor populations within the forming LPM. Combining gene expression analysis and imaging of transgenic reporter zebrafish embryos, we chart the origin of mesothelial progenitors to the lateral-most, hand2-expressing LPM and confirm evolutionary conservation in mouse. Our time-lapse imaging of transgenic hand2 reporter embryos captures zebrafish mesothelium formation, documenting the coordinated cell movements that form pericardium and visceral and parietal peritoneum. We establish that the primordial germ cells migrate associated with the forming mesothelium as ventral migration boundary. Functionally, hand2 mutants fail to close the ventral mesothelium due to perturbed migration of mesothelium progenitors. Analyzing mouse and human mesothelioma tumors hypothesized to emerge from transformed mesothelium, we find de novo expression of LPM-associated transcription factors, and in particular of Hand2, indicating the re-initiation of a developmental transcriptional program in mesothelioma. Taken together, our work outlines a genetic and developmental signature of mesothelial origins centered around Hand2, contributing to our understanding of mesothelial pathologies and mesothelioma.

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The cooperation between HAND2 and MYCN on DNA binding [HAND2-overexpression_ChIPseq]

Project description:HAND2 assists MYCN bind to DNA.

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