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Nuclear factor Y-mediated H3K27me3 demethylation of the SOC1 locus orchestrates flowering responses of Arabidopsis
The onset of flowering is a major developmental transition in plants. Here, Hou et al. show that a NF-Y transcription factor complex exerts epigenetic control over the timing of flowering in Arabidopsisby modulating trimethylated H3K27 levels at a floral pathway integrator, SOC1, in response to environmental and intrinsic signals.
- Xingliang Hou
- , Jiannan Zhou
- & Hao Yu
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| Open AccessMatrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression
Soft 3D gels can promote the growth of tumour-repopulating cells, a self-renewing subpopulation of cancer cells critical in cancer progression. Here, the authors investigate the mechanism behind this phenomenon and show that the histone 3 lysine residue 9 methylation and Sox2 are controlling this process.
- Youhua Tan
- , Arash Tajik
- & Ning Wang
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miR-508 sustains phosphoinositide signalling and promotes aggressive phenotype of oesophageal squamous cell carcinoma
The negative regulatory effects of phosphatases are sometimes altered in cancer, but the mechanisms that mediate this effect remain undefined. Here, the authors show that miR-508 suppresses multiple phosphatases, resulting in constitutive activation of the PI3K/Akt pathway.
- Chuyong Lin
- , Aibin Liu
- & Libing Song
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Differentiation-dependent requirement of Tsix long non-coding RNA in imprinted X-chromosome inactivation
Imprinted mouse X-chromosome inactivation is controlled by two long non-coding RNAs, Tsix and Xist. Here, Maclary et al. demonstrate that Tsix is dispensable during the initiation and maintenance of X-inactivation in vivo and in vitro, but required to prevent Xist expression as trophectodermal progenitors differentiate.
- Emily Maclary
- , Emily Buttigieg
- & Sundeep Kalantry
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Natural occurring epialleles determine vitamin E accumulation in tomato fruits
Selecting for varieties of commercial crops with enhanced nutritional quality is important in agriculture. Here, the authors identify alleles of a gene in tomatoes that give rise to increased levels of vitamin E and find that the promoter of the gene is differentially methylated.
- Leandro Quadrana
- , Juliana Almeida
- & Fernando Carrari
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| Open AccessSnf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
The chromatin remodelling proteins Snf2h and Snf2l regulate nucleosome spacing. Here, the authors show that Snf2hablation impairs chromatin organization of neuronal lineages during mouse embryonic and post-natal cerebellar development.
- Matías Alvarez-Saavedra
- , Yves De Repentigny
- & David J. Picketts
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Control of early seedling development by BES1/TPL/HDA19-mediated epigenetic regulation of ABI3
In plants, brassinosteroids (BR) counter the suppressive effect of abscisic acid (ABA) on early seedling development. Ryu et al.show that ABA regulator genes are suppressed by a complex containing the BR-activated protein BES1, a histone deacetylase, and the transcriptional corepressor TOPLESS.
- Hojin Ryu
- , Hyunwoo Cho
- & Ildoo Hwang
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A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice
DNA double strand breaks are repaired by nonhomologous end-joining (NHEJ) or homologous recombination (HR) pathways. Here, Pai et al.discover that post-translational modification of lysine 36 of histone H3 plays a key role in determining double strand repair pathway choice.
- Chen-Chun Pai
- , Rachel S. Deegan
- & Timothy C. Humphrey
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Overproduction of stomatal lineage cells in Arabidopsis mutants defective in active DNA demethylation
Loss of active DNA demethylation increases DNA methylation at numerous loci in plant vegetative tissues; however, resulting developmental phenotypes have not been observed. Yamamuro et al. show that mutation of the 5-methylcytosine DNA glycosylase ROS1 results in overproduction of stomatal lineage cells in Arabidopsis.
- Chizuko Yamamuro
- , Daisuke Miki
- & Jian-Kang Zhu
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| Open AccessPADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation
Peptidylarginine deiminase 4 (PADI4) is a transcriptional co-regulator that converts arginine residues at histone tails to citrulline. The authors show that PADI4 interacts with the central haematopoietic transcription factor TAL1 to regulate gene expression in an erythroleukemia cell line.
- Stephan Kolodziej
- , Olga N. Kuvardina
- & Jörn Lausen
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| Open AccessMaternal nutrition at conception modulates DNA methylation of human metastable epialleles
Maternal diet affects DNA methylation in the developing offspring, leading to phenotypic changes. Here, Dominguez-Salas et al. exploit seasonal variation in the diet of Gambian women to show that maternal methyl donor nutrient status around the time of conception predicts methylation levels at metastable epialleles in infants.
- Paula Dominguez-Salas
- , Sophie E. Moore
- & Branwen J. Hennig
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IKKα restoration via EZH2 suppression induces nasopharyngeal carcinoma differentiation
Nasopharyngeal carcinomas often present as undifferentiated tumours. Here, Yan et al. show that reduced expression of IKK via promoter methylation results in the undifferentiated phenotype of the tumours and that treatment with retinoic acid can reverse these features.
- Min Yan
- , Yan Zhang
- & Quentin Liu
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| Open AccessA DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
Defective proteins or functional proteins that are no longer needed can be degraded in the endoplasmic reticulum. In this study, Lopez-Serra et al.show that DERL3, which is involved in protein degradation in the endoplasmic reticulum, is aberrantly silenced in cancer, leading to activation of a glucose transporter and dysregulated glycolysis.
- Paula Lopez-Serra
- , Miguel Marcilla
- & Manel Esteller
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PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system
Epigenetic codes translate external stimuli into targeted and long-lasting gene regulation. In this study, the authors show that regenerative retrograde signalling activates the epigenetic modifying enzyme PCAF, inducing gene expression and promoting axon regeneration in a mouse spinal cord injury model.
- Radhika Puttagunta
- , Andrea Tedeschi
- & Simone Di Giovanni
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| Open AccessEpigenetic plasticity of Cd8a locus during CD8+ T-cell development and effector differentiation and reprogramming
CD8 expression levels on peripheral CD8+ T cells are regulated during development and effector differentiation. Here, the authors show that methylation patterns at the Cd8a locus, whose product is essential for surface CD8 expression, can change during T-cell development, activation, cytokine polarization and reprogramming.
- Kim L. Harland
- , E. Bridie Day
- & Anne Kelso
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| Open AccessDifferential methylation of the TRPA1 promoter in pain sensitivity
Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1is associated with pain sensitivity in humans.
- J.T. Bell
- , A.K. Loomis
- & T.D. Spector
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The central role of EED in the orchestration of polycomb group complexes
Polycomb group proteins are epigenetic gene silencers that are thought to exist in two biochemically distinct multiprotein complexes, termed PRC-1 and -2. Here, Cao et al.show that EED, a core component of PRC2, interacts with and functions as part of PRC1, thus coordinating the activities of both complexes.
- Qi Cao
- , Xiaoju Wang
- & Arul M. Chinnaiyan
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| Open AccessLow paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes
Paternal diet has been shown to influence the metabolism of offspring in rats and mice. Here Lambrot et al.report DNA and histone methylation changes in the sperm of male mice on a folate-deficient diet and observe developmental defects in their offspring.
- R. Lambrot
- , C. Xu
- & S. Kimmins
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Stepwise histone modifications are mediated by multiple enzymes that rapidly associate with nascent DNA during replication
Chromatin marks have to be re-established after DNA replication. Here Petruk et al. show that many histone-modifying enzymes are found in close proximity to newly replicated DNA in cells of Drosophilaembryos before the corresponding histone marks are re-established.
- Svetlana Petruk
- , Kathryn L. Black
- & Alexander Mazo
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RNA editing regulates transposon-mediated heterochromatic gene silencing
The Hoppel transposable element mediates heterochromatin formation in Drosophila. Here Savva et al. report that the RNA-editing enzyme, ADAR, edits a long double-stranded RNA generated by the Hoppeltransposon, thereby regulating heterochromatin formation and gene expression.
- Yiannis A. Savva
- , James E. C. Jepson
- & Robert A. Reenan
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Involvement of parental imprinting in the antisense regulation of onco-miR-372-373
The miR-372-3 cluster has a role in oncogenesis. In this study, by utilizing parthenogenetic induced pluripotent stem cells, that lack the paternal genome, Stelzer et al.report that these miR-372-3 are negatively regulated by a paternally imprinted antisense transcript and that loss of its expression promotes oncogenesis.
- Yonatan Stelzer
- , Ido Sagi
- & Nissim Benvenisty
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Semiconductor-based DNA sequencing of histone modification states
Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.
- Christine S. Cheng
- , Kunal Rai
- & Ido Amit
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PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine
Tet proteins control DNA demethylation, but how the DNA target regions are determined is unclear. Here the authors report that during adipocyte differentiation, PPARγ binds to the PPAR-response element and recruits Tet proteins, thereby inducing local DNA demethylation.
- Katsunori Fujiki
- , Akihiro Shinoda
- & Masayuki Murata
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Dissecting the role of H3K64me3 in mouse pericentromeric heterochromatin
H3K64 trimethylation on the nucleosome lateral surface marks pericentric heterochromatin. Here Lange et al.show that H3K64me3 enrichment ensures heterochromatin integrity and occurs in an H3K9me3-dependent, but an H4K20me3- and heterochromatin protein 1-independent manner.
- Ulrike C. Lange
- , Stéphanie Siebert
- & Robert Schneider
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Measurement of acetylation turnover at distinct lysines in human histones identifies long-lived acetylation sites
Dynamic changes in histone acetylation are associated with regulation of gene expression. Zheng and colleagues develop a metabolic labelling technique that facilitates the measurement of acetylation turnover rates, and identify a group of sites whose acetylation is remarkably stable.
- Yupeng Zheng
- , Paul M. Thomas
- & Neil L. Kelleher
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DNA unmethylome profiling by covalent capture of CpG sites
Chemical modifications of CpG dinucleotides form part of the epigenetic code and various methods for the detection of modified CpG sites exist. Here Kriukiene and colleagues report a complementary method that allows the profiling of unmodified CpG sites within the genome, which they call the 'unmethylome'.
- Edita Kriukienė
- , Viviane Labrie
- & Saulius Klimašauskas
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| Open AccessInsights into the role of DNA methylation in diatoms by genome-wide profiling in Phaeodactylum tricornutum
Genome-wide maps of DNA methylation have so far been restricted to plants, animals and fungi. Here, the authors report the first whole-genome methylome of a stramenopile, the diatom Phaeodactylum tricornatum, and provide insight into the evolution of DNA methylation in eukaryotes.
- Alaguraj Veluchamy
- , Xin Lin
- & Leïla Tirichine
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Dynamics of 5-hydroxymethylcytosine during mouse spermatogenesis
Changes in DNA methylation during mammalian spermatogenesis are poorly understood. The authors show that the content of 5-hydroxymethylcytosine, a stable intermediate of DNA demethylation, changes dynamically during mouse spermatogenesis and is associated with functional genomic regions and transcription.
- Haiyun Gan
- , Lu Wen
- & Fuchou Tang
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Max is a repressor of germ cell-related gene expression in mouse embryonic stem cells
Even though both embryonic stem cells and primordial germ cells express pluripotency markers, they differ in their developmental potential. Maeda et al. show that, in embryonic stem cells, the Myc family member Max mediates epigenetic repression of genes involved in germ cell development.
- Ikuma Maeda
- , Daiji Okamura
- & Yasuhisa Matsui
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UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9
Epigenetic inheritance of DNA methylation requires the recruitment of DNA methyltransferase activity to the replication fork by UHRF1. Liu et al. show that optimal association of UHRF1 with the replication fork and resulting DNA methylation requires two domains that bind hemi-methylated DNA and methylated histones, respectively.
- Xiaoli Liu
- , Qinqin Gao
- & Jiemin Wong
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| Open AccessSir2a regulates rDNA transcription and multiplication rate in the human malaria parasite Plasmodium falciparum
The factors that modulate growth rate of the human malaria parasite Plasmodium falciparum remain poorly understood. Here Scherf and collaborators demonstrate that the Plasmodiumsirtuin PfSir2a regulates the transcription of ribosomal DNA, thereby modulating parasite proliferation rate and virulence.
- Liliana Mancio-Silva
- , Jose Juan Lopez-Rubio
- & Artur Scherf
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| Open AccessTransgenerational gene silencing causes gain of virulence in a plant pathogen
Plant pathogens encode effector proteins that trigger immunity in plants carrying appropriate resistance genes. Here Qutob et al. show non-Mendelian interactions between naturally occurring Phytophthora sojaealleles that result in transgenerational gene silencing and gain of virulence in soybean plants.
- Dinah Qutob
- , B. Patrick Chapman
- & Mark Gijzen
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Detection and differential diagnosis of colon cancer by a cumulative analysis of promoter methylation
Changes in the methylation pattern of gene promoters are hallmarks of certain cancers, such as colon cancer. Here Yang et al.identify and validate a set of genes and measure the cumulative methylation of promoters, which allows them to distinguish between two stages of colon cancer.
- Qiong Yang
- , Ying Dong
- & Shu Wang
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| Open AccessThyroid hormone determines the start of the sensitive period of imprinting and primes later learning
Filial imprinting allows precocial birds to form social attachment to other animals or objects soon after hatching. Yamaguchi and colleagues investigate the mechanisms responsible for this, and find that thyroid hormones circulating in the plasma regulate the sensitive period during which imprinting occurs.
- Shinji Yamaguchi
- , Naoya Aoki
- & Koichi J. Homma
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| Open AccessHigh-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring
Environmental factors can influence one's susceptibility to cancer, but it is not clear whether such an influence extends beyond the directly exposed generations. Here, feeding pregnant rats with a high-fat diet or a hormone derivative, the authors observe increased breast cancer risk in up to three subsequent generations.
- Sonia de Assis
- , Anni Warri
- & Leena Hilakivi-Clarke
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Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation
Chromatin in embryonic stem cells is present in an open state presumably to facilitate gene expression changes required for pluripotency and subsequent multilineage differentiation. This study describes roles for lamin A, histone acetylation and G9a-mediated histone H3 lysine 9 methylation in regulating chromatin plasticity in these cells.
- Shai Melcer
- , Hadas Hezroni
- & Eran Meshorer
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Genomics of DNA cytosine methylation in Escherichia coli reveals its role in stationary phase transcription
How DNA cytosine methylation affects gene expression inEscherichia coli is poorly understood. Here, the first genome-wide study of cytosine methylation in E. coliat single-base resolution reveals that cytosine methylation controls the expression of genes during the stationary growth phase.
- Christina Kahramanoglou
- , Ana I. Prieto
- & Aswin S.N. Seshasayee
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An atlas of DNA methylomes in porcine adipose and muscle tissues
Epigenetic and genetic factors have a role in obesity but the role of epigenetics in this disease is unclear. Here, Liet al. investigated global DNA methylation patterns in three breeds of pigs that have different fat contents, providing a resource for the further analysis of differentially methylated gene promoters in obesity.
- Mingzhou Li
- , Honglong Wu
- & Ruiqiang Li
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Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster
Hox gene expression is induced upon cellular differentiation and is inhibited in pluripotent cells. Bocker and colleagues show that the maintenance of induced transcription depends on Tet2 mediated hydroxylation of 5-methylcytosine at theHoxagene locus, indicating that this epigenetic switch is required for an active chromatin state and gene expression.
- Michael T. Bocker
- , Francesca Tuorto
- & Achim Breiling
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| Open AccessFAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure
Lysine-specific demethylase 1 (LSD1) removes methyl groups from mono-methylated and dimethylated lysine 4 of histone H3 and represses transcription. In this study, a role for LSD1 in the regulation of genes involved in energy expenditure in adipocytes is reportedin vitroand in mice fed on a high-fat diet.
- Shinjiro Hino
- , Akihisa Sakamoto
- & Mitsuyoshi Nakao
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MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a
The methylation of DNA and histone H3 lysine 9 in chromatin are positively correlated. This study shows that the DNA methyl transferase Dnmt3a is methylated, and a crystal structure of Dnmt3a bound to the chromodomain protein MPP8 suggests a molecular mechanism.
- Yanqi Chang
- , Lidong Sun
- & Xiaodong Cheng
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SIRT6 is required for maintenance of telomere position effect in human cells
Chromatin is rendered silent by epigenetic marks when in proximity to telomeres, and, in yeast, this effect requires the histone-modifying enzyme Sir2. In this study, the human Sir2 family member SIRT6 is shown to modulate the telomere position effect in human cells.
- Ruth I. Tennen
- , Dennis J. Bua
- & Katrin F. Chua
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| Open AccessCytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni
The chronic disease schistosomiasis is caused by the blood flukeSchistosoma mansoni. By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.
- Kathrin K. Geyer
- , Carlos M. Rodríguez López
- & Karl F. Hoffmann
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| Open AccessToxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells
Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.
- Monika Raab
- , Sven Kappel
- & Klaus Strebhardt
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5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming
Pronucleus DNA becomes demethylated during zygotic development. Here, the authors demonstrate that the reduction in 5-methylcytosine levels is accompanied by an increase in the presence of 5-hydroxymethylcytosine, and suggest that this has a role in developmental reprogramming.
- Mark Wossidlo
- , Toshinobu Nakamura
- & Jörn Walter
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| Open AccessHistone acetylation controls the inactive X chromosome replication dynamics
How one copy of the X chromosome is silenced in replicating female somatic cells is poorly understood. Here, the authors demonstrate that the inactive X chromosome is replicated before constitutive heterochromatin and that histone hypoacetylation has a role in controlling replication of the inactive X chromosome.
- Corella S. Casas-Delucchi
- , Alessandro Brero
- & M. Cristina Cardoso
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| Open AccessChromatin remodelling complex dosage modulates transcription factor function in heart development
Inherited congenital heart defects are prevalent in the human population, but the molecular mechanisms are poorly understood. In this article, deficiency in the chromatin remodelling factor, Brg1, is shown to alter cardiac development in both mouse and zebrafish laboratory models.
- Jun K. Takeuchi
- , Xin Lou
- & Benoit G. Bruneau
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Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes
Pseudogenes are prevalent in the human genome; however, their biological function is relatively unknown. In this study, the high mobility group A1 (HMGA1) pseudogene is shown to destabilizeHMGA1 mRNA. These findings have implications for diabetes, as two patients are reported to express high levels of the HMGA1pseudogene.
- Eusebio Chiefari
- , Stefania Iiritano
- & Antonio Brunetti