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Article
Open AccessGLIS3 expression in the thyroid gland in relation to TSH signaling and regulation of gene expression
Loss of GLI-Similar 3 (GLIS3) function in mice and humans causes congenital hypothyroidism (CH). In this study, we demonstrate that GLIS3 protein is first detectable at E15.5 of murine thyroid development, a t...
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Article
Open AccessGLIS3 regulates transcription of thyroid hormone biosynthetic genes in coordination with other thyroid transcription factors
Loss of the transcription factor GLI-Similar 3 (GLIS3) function causes congenital hypothyroidism (CH) in both humans and mice due to decreased expression of several thyroid hormone (TH) biosynthetic genes in thyr...
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Article
Open AccessCD11b+ lung dendritic cells at different stages of maturation induce Th17 or Th2 differentiation
Dendritic cells (DC) in the lung that induce Th17 differentiation remain incompletely understood, in part because conventional CD11b+ DCs (cDC2) are heterogeneous. Here, we report a population of cDCs that rapidl...
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Article
Open AccessGLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans
Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open-angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of...
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Article
Open AccessDNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation
DNA methylation and trimethylated histone H4 Lysine 20 (H4K20me3) constitute two important heterochromatin-enriched marks that frequently cooperate in silencing repetitive elements of the mammalian genome. How...
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Article
Open AccessInteraction of the pioneer transcription factor GATA3 with nucleosomes
During cellular reprogramming, the pioneer transcription factor GATA3 binds chromatin, and in a context-dependent manner directs local chromatin remodeling and enhancer formation. Here, we use high-resolution ...
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Article
Open AccessComprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms
Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular ...
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Article
Open AccessAlterations in promoter interaction landscape and transcriptional network underlying metabolic adaptation to diet
Metabolic adaptation to nutritional state requires alterations in gene expression in key tissues. Here, we investigated chromatin interaction dynamics, as well as alterations in cis-regulatory loci and transcr...
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Article
Open AccessRUNX1 maintains the identity of the fetal ovary through an interplay with FOXL2
Sex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian pre-granulosa cells or testicular Sertoli cells. This fate specification hinges on a balance of tr...
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Article
Open AccessDNA methylation in mice is influenced by genetics as well as sex and life experience
DNA methylation is an essential epigenetic process in mammals, intimately involved in gene regulation. Here we address the extent to which genetics, sex, and pregnancy influence genomic DNA methylation by inte...
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Article
Open AccessDosage compensation and DNA methylation landscape of the X chromosome in mouse liver
DNA methylation plays a key role in X-chromosome inactivation (XCI), a process that achieves dosage compensation for X-encoded gene products between mammalian female and male cells. However, differential sex c...
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Article
Open AccessLoss of Glis3 causes dysregulation of retrotransposon silencing and germ cell demise in fetal mouse testis
Fetal germ cell development is regulated by an elaborate combination of cell-extrinsic and cell-intrinsic signals. Here we identify a novel role for the Krüppel-like transcription factor Gli-Similar 3 (Glis3) in ...
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Article
Open AccessMuver, a computational framework for accurately calling accumulated mutations
Identification of mutations from next-generation sequencing data typically requires a balance between sensitivity and accuracy. This is particularly true of DNA insertions and deletions (indels), that can impa...
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Article
Open AccessGATA3 zinc finger 2 mutations reprogram the breast cancer transcriptional network
GATA3 is frequently mutated in breast cancer; these mutations are widely presumed to be loss-of function despite a dearth of information regarding their effect on disease course or their mechanistic impact on ...
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Article
Open AccessAn obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression
The gut microbiome, a key constituent of the colonic environment, has been implicated as an important modulator of human health. The eukaryotic epigenome is postulated to respond to environmental stimuli throu...
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Article
The novel p53 target TNFAIP8 variant 2 is increased in cancer and offsets p53-dependent tumor suppression
Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a stress-response gene that has been associated with cancer, but no studies have differentiated among or defined the regulation or function of any of its sev...
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Article
Open AccessGATA3-dependent cellular reprogramming requires activation-domain dependent recruitment of a chromatin remodeler
Transcription factor-dependent cellular reprogramming is integral to normal development and is central to production of induced pluripotent stem cells. This process typically requires pioneer transcription fac...
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Article
Open AccessBreast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover
The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-α (ERα)-positive breast tumors in which it participates with ERα and FOXA1 in a complex transcriptional regulatory progra...
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Article
An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers
Dmitry Gordenin, Gad Getz and colleagues report an analysis of mutation patterns in cancer genomes and find evidence of mutagenesis induced by APOBEC cytidine deaminase enzymes. They find an APOBEC mutagenesis...
