Parental imprinting results in a monoallelic parent-of-origin dependent gene expression. However, many imprinted genes identified by differential methylation do not exhibit complete monoallelic expression. Previous studies demonstrated a complex tissue-dependent expression patterns for some imprinted genes. Still, the complete magnitude of this phenomenon remains largely unknown. Differentiating human parthenogenetic induced pluripotent stem cells into different cell types and combining DNA methylation with novel 5' RNA sequencing methodology, enabled us to identify tissue- and isoform-dependent imprinted genes in a genome wide manner. We show that nearly half of all imprinted genes expresses both biallelic and monoallelic isoforms, that are controlled by tissue specific alternative promoters. This study provides the first global analysis of tissue-specific imprinting in humans, and implies that alternative promoters are central in the regulation of imprinted genes.
No associated publication
Sex, Cell line
View SamplesComparison of gene expression of cancerous and non cancerous lung adenocarcinoma tissue. Tumour and normal samples from 18 patients plus tumour only from 5 patients.
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Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesThree parthenogenetic induced pluripotent stem cell (PgHiPSCs) lines were generated from each of the ovarian teratoma cell lines (two distinct individuals). Two normal iPS cell lines were generated from normal fibroblasts. Three biological replicates of normal embryonic stem cells (H9, HESCs) were perfomed.
Global analysis of parental imprinting in human parthenogenetic induced pluripotent stem cells.
Sex, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Specimen part, Cell line, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.
Specimen part, Cell line
View SamplesWe used microarrays to identify the gene expression changes in Cbx1-/- (HP1beta) knockout embryonic stem cells (ESCs) and Cbx5-/- (HP1alpha) knockout ESCs compared to WT ESCs and in embryoid bodies (EBs) differentiated from those three ESC types.
Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.
Specimen part, Cell line
View SamplesWe used microarrays to identify the gene expression changes after Smarcd1 knockdown in ESCs and 4 day RA differentiated ESCs
Differential association of chromatin proteins identifies BAF60a/SMARCD1 as a regulator of embryonic stem cell differentiation.
Specimen part
View SamplesTo identify early processes in carcinogenesis, we used an in vitro model, based on the initiating event in cervical cancer, human papillomavirus (HPV) transformation of keratinocytes. We compared gene expression in primary keratinocytes (K) and HPV16-transformed keratinocytes from early (E) and late (L) passages, and from benzo[a]pyrene treated L cells (BP). The transformed cells exhibit similar transcriptional changes to clinical cervical carcinoma. We revealed a contraction in expression of the apoptotic network during HF1 cell transformation, which affected the ability of L and BP cells to execute apoptosis, but did not lead to resistance to apoptotic stimuli. The contraction in the apoptotic machinery during the process of transformation was accompanied by a switch from apoptosis to necrosis in response to CDDP. The shrinkage of the pro- and anti-apoptotic networks appears to be part of a general contraction in the number of genes transcribed in L and BP cells. We also identified a large group of genes with induced expression, which are involved in cell metabolism and cell cycle, suggesting increased investment of the transformed cell in cellular proliferation. We hypothesize that the decrease in expression of many diverse pathways, including the pro- and anti-apoptotic networks, cuts the energy requirements for cell maintenance, allowing energy to be diverted towards rapid cell proliferation. This study supports the hypothesis that the process of cancer transformation may be accompanied by a shift from apoptosis to necrosis.
Shift from apoptotic to necrotic cell death during human papillomavirus-induced transformation of keratinocytes.
Specimen part, Cell line
View SamplesDuring early development before gonadal differentiation, sex chromosomes are the main difference between males and females. We examined any genetically driven sex dimorphisms in human pluripotent stem cells focusing on Y chromosome contribution.
Sex-dependent gene expression in human pluripotent stem cells.
Sex, Specimen part
View SamplesChromosomal instability in early cancer stages is caused by stress on DNA replication. The molecular basis for replication perturbation in this context is currently unknown. We studied the replication dynamics in cells in which a regulator of S-phase entry and cell proliferation, the Rb-E2F pathway, is aberrantly activated. Aberrant activation of this pathway by HPV-16 E6/E7 or cyclin E oncogenes, significantly decreased the cellular nucleotide levels in the newly transformed cells. Exogenously supplied nucleosides rescued the replication stress and DNA damage, and dramatically decreased oncogene-induced transformation. Increased transcription of nucleotide biosynthesis genes, mediated by expressing the transcription factor c-Myc, increased the nucleotide pool and also rescued the replication-induced DNA damage. Our results suggest a model for early oncogenesis in which uncoordinated activation of factors regulating cell proliferation leads to insufficient nucleotides that fail to support normal replication and genome stability.
Nucleotide deficiency promotes genomic instability in early stages of cancer development.
Sex, Specimen part
View Samples