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https://www.readbyqxmd.com/read/29101321/contribution-of-epigenetic-landscapes-and-transcription-factors-to-x-chromosome-reactivation-in-the-inner-cell-mass
#1
Maud Borensztein, Ikuhiro Okamoto, Laurène Syx, Guillaume Guilbaud, Christel Picard, Katia Ancelin, Rafael Galupa, Patricia Diabangouaya, Nicolas Servant, Emmanuel Barillot, Azim Surani, Mitinori Saitou, Chong-Jian Chen, Konstantinos Anastassiadis, Edith Heard
X-chromosome inactivation is established during early development. In mice, transcriptional repression of the paternal X-chromosome (Xp) and enrichment in epigenetic marks such as H3K27me3 is achieved by the early blastocyst stage. X-chromosome inactivation is then reversed in the inner cell mass. The mechanisms underlying Xp reactivation remain enigmatic. Using in vivo single-cell approaches (allele-specific RNAseq, nascent RNA-fluorescent in situ hybridization and immunofluorescence), we show here that different genes are reactivated at different stages, with more slowly reactivated genes tending to be enriched in H3meK27...
November 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/29075464/exchange-of-genetic-information-between-therian-x-and-y-chromosome-gametologs-in-old-evolutionary-strata
#2
Peter Peneder, Barbara Wallner, Claus Vogl
Therian X and Y sex chromosomes arose from a pair of autosomes. Y chromosomes consist of a pseudoautosomal region that crosses over with the X chromosome and a male-specific Y-chromosomal region that does not. The X chromosome can be structured into "evolutionary strata". Divergence of X-chromosomal genes from their gametologs is similar within a stratum, but differs among strata, likely caused by a different onset of suppression of crossing over between gametologs. After stratum formation, exchange of information between gametologs has long been believed absent; however, recent studies have shown limited exchange, likely through gene conversion...
October 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/29073101/utx-guided-neural-crest-function-underlies-craniofacial-features-of-kabuki-syndrome
#3
Karl B Shpargel, Joshua Starmer, Chaochen Wang, Kai Ge, Terry Magnuson
Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D). However, the cellular and molecular etiology of histone-modifying enzymes in craniofacial disorders is unknown. We now establish Kabuki syndrome as a neurocristopathy, whereby the majority of clinical features are modeled in mice carrying neural crest (NC) deletion of UTX, including craniofacial dysmorphism, cardiac defects, and postnatal growth retardation...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29070530/the-histone-demethylase-jumonji-domain-containing-protein-3-jmjd3-regulates-fibroblast-activation-in-systemic-sclerosis
#4
Christina Bergmann, Amelie Brandt, Benita Merlevede, Ludwig Hallenberger, Clara Dees, Thomas Wohlfahrt, Sebastian Pötter, Yun Zhang, Chih-Wei Chen, Tatiana Mallano, Ruifang Liang, Rosebeth Kagwiria, Alexander Kreuter, Ioanna Pantelaki, Aline Bozec, David Abraham, Ralf Rieker, Andreas Ramming, Oliver Distler, Georg Schett, Jörg H W Distler
OBJECTIVES: Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis...
October 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29045832/utx-kdm6a-loss-enhances-the-malignant-phenotype-of-multiple-myeloma-and-sensitizes-cells-to-ezh2-inhibition
#5
Teresa Ezponda, Daphné Dupéré-Richer, Christine M Will, Eliza C Small, Nobish Varghese, Tej Patel, Behnam Nabet, Relja Popovic, Jon Oyer, Marinka Bulic, Yupeng Zheng, Xiaoxiao Huang, Mrinal Y Shah, Sayantan Maji, Alberto Riva, Manuela Occhionorelli, Giovanni Tonon, Neil Kelleher, Jonathan Keats, Jonathan D Licht
Loss or inactivation of the histone H3K27 demethylase UTX occurs in several malignancies, including multiple myeloma (MM). Using an isogenic cell system, we found that loss of UTX leads to deactivation of gene expression ultimately promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of MM cells. Moreover, UTX mutant cells showed increased in vitro and in vivo sensitivity to inhibition of EZH2, a histone methyltransferase that generates H3K27me3. Such sensitivity was related to a decrease in the levels of IRF4 and c-MYC and an activation of repressors of IRF4 characteristic of germinal center B cells such as BCL6 and IRF1...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29031004/starting-a-uterus-transplantation-service-notes-from-a-small-island
#6
Hak-Koon Tan, Bien-Keem Tan, Lay-Kok Tan, Jan I Olofsson, Pernilla Dahm-Kähler, Mats Brännström
Once thought as an impossibility, uterus transplantation (UTx) is now very much a reality and is being offered as a clinical service in several countries, including Sweden that pioneered this new field of infertility treatment with their initial clinical trial in 2013. (1) A majority of the women in that trial has given birth to one or more babies. Unlike conventional solid organ transplantation, UTx is an ephemeral transplant: the sole purpose of grafting the uterus is for the recipient to conceive and have offspring and the uterus can then be removed...
October 14, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/29024911/simultaneous-quantitative-analysis-of-uremic-toxins-by-lc-ms-ms-with-a-reversed-phase-cation-exchange-anion-exchange-tri-modal-mixed-mode-column
#7
Yoshitomi Kanemitsu, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Daisuke Saigusa, Chikahisa Mukawa, Tatsuki Tachikawa, Takaaki Abe, Yoshihisa Tomioka
Column choice is crucial to the development of liquid chromatography/tandem mass spectrometry (LC-MS/MS) methods because analyte selectivity is dependent on the nature of the stationary phase. Recently, mixed-mode chromatography, which employs a combination of two or more stationary phases and solvent systems, has emerged as an alternative to multiple, complementary, single-column systems. This report describes the development and validation of a novel analytical method based on LC-MS/MS employing a reversed-phase/cation-exchange/anion-exchange tri-modal column (Scherzo SS-C18; Imtakt) for the simultaneous quantification of various uremic toxins (UTx), including creatinine, 1-methyladenosine, trimethylamine-N-oxide, indoxyl sulfate, p-cresyl sulfate, phenyl sulfate and 4-ethylphenyl sulfate...
October 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28977932/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#8
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970783/the-histone-h3k27-demethylase-utx-regulates-synaptic-plasticity-and-cognitive-behaviors-in-mice
#9
Gang-Bin Tang, Yu-Qiang Zeng, Pei-Pei Liu, Ting-Wei Mi, Shuang-Feng Zhang, Shang-Kun Dai, Qing-Yuan Tang, Lin Yang, Ya-Jie Xu, Hai-Liang Yan, Hong-Zhen Du, Zhao-Qian Teng, Feng-Quan Zhou, Chang-Mei Liu
Histone demethylase UTX mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish a mechanistic switch to activate large sets of genes. Mutation of Utx has recently been shown to be associated with Kabuki syndrome, a rare congenital anomaly syndrome with dementia. However, its biological function in the brain is largely unknown. Here, we observe that deletion of Utx results in increased anxiety-like behaviors and impaired spatial learning and memory in mice. Loss of Utx in the hippocampus leads to reduced long-term potentiation and amplitude of miniature excitatory postsynaptic current, aberrant dendrite development and defective synapse formation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28952292/triptolide-promotes-senescence-of-prostate-cancer-cells-through-histone-methylation-and-heterochromatin-formation
#10
Ousman Tamgue, Ming Lei
Background: Triptolide is a medicinal herb-derived diterpene triepoxide with potent anti-tumor activity, mainly ,correlated with its ability to inhibit and inactivate subunits of RNA polymerase II, thereby suppressing global gene transcription. Epigenetic imbalance including histone methylation are well known to play important roles in prostate cancer (PCa) onset and progression. The goal of this study was to investigate whether triptolide might exert anti-PCa influence by reshaping the histone methylation landscape...
September 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28930707/re-evaluating-the-ethics-of-uterine-transplantation
#11
Danish Zaidi
In February 2016, the Cleveland Clinic initiated the first attempt at cadaveric uterine transplantation (UTx) in the United States. The transplantation was ultimately unsuccessful, but it opened doors for further research on both live and cadaveric UTx. While initial strides toward successful transplantation have been made, questions persist on the ethics of UTx: whether the uterus is a vital organ, whether we should prioritize live or cadaveric options, and how the procedure should be covered by health insurance...
2017: Journal of Clinical Ethics
https://www.readbyqxmd.com/read/28928876/heterochromatin-reduction-correlates-with-the-increase-of-the-kdm4b-and-kdm6a-demethylases-and-the-expression-of-pericentromeric-dna-during-the-acquisition-of-a-transformed-phenotype
#12
Cinthya Gurrion, Maritere Uriostegui, Mario Zurita
Cancer cells have alterations in chromatin organization, mostly a reduction in heterochromatin. How this process occurs during transformation and if it participates in the maintenance of a cancerous phenotype is not well understood. Here, using a transformation-inducible cell line, we analyzed the changes that occur in heterochromatin during transformation to a cancerous phenotype. After transformation, there is a reduction in heterochromatin bodies and a nuclear reorganization of HP1α. These occurrences correlate with reductions in H3K9me3 and H3K27me3 levels and with some of the enzymes that introduce these modifications...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28880717/bivalent-histone-codes-on-wnt5a-during-odontogenic-differentiation
#13
Y Zhou, L Zheng, F Li, M Wan, Y Fan, X Zhou, W Du, C Pi, D Cui, B Zhang, J Sun, X Zhou
Lineage-committed differentiation is an essential biological program during odontogenesis, which is tightly regulated by lineage-specific genes. Some of these genes are modified by colocalization of H3K4me3 and H3K27me3 marks at promoter regions in progenitors. These modifications, named "bivalent domains," maintain genes in a poised state and then resolve for later activation or repression during differentiation. Wnt5a has been reported to promote odontogenic differentiation in dental mesenchyme. However, relatively little is known about the epigenetic modulations on Wnt5a activation during tooth development...
September 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28732206/a-utx-mll4-p300-transcriptional-regulatory-network-coordinately-shapes-active-enhancer-landscapes-for-eliciting-transcription
#14
Shu-Ping Wang, Zhanyun Tang, Chun-Wei Chen, Miho Shimada, Richard P Koche, Lan-Hsin Wang, Tomoyoshi Nakadai, Alan Chramiec, Andrei V Krivtsov, Scott A Armstrong, Robert G Roeder
Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1(+)/H3K27ac(+)) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#15
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28683576/womb-transplants-with-live-births-an-update-and-the-future
#16
Mats Brännström
Absolute uterine factor infertility, with a uterine absence or presence of a nonfunctional uterus, has during the last decades been the only remaining, major group of female infertility. Uterus transplantation (UTx) has now emerged as the first therapy for these women that have traditionally been regarded as unconditionally infertile. Areas covered: This review summarizes the research preparations in several experimental animal species that paved the way for the clinical introduction of UTx. The article also describes the human UTx attempts that have been reported up until today and the several live births that have occurred after the initial UTx baby was born in 2014...
July 6, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28669924/histone-h3-lysine-4-methyltransferase-kmt2d
#17
REVIEW
Eugene Froimchuk, Younghoon Jang, Kai Ge
Histone-lysine N-methyltransferase 2D (KMT2D), also known as MLL4 and MLL2 in humans and Mll4 in mice, belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein over 5500 amino acids in size and is partially functionally redundant with KMT2C. KMT2D is widely expressed in adult tissues and is essential for early embryonic development. The C-terminal SET domain is responsible for its H3K4 methyltransferase activity and is necessary for maintaining KMT2D protein stability in cells...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28609280/the-history-behind-successful-uterine-transplantation-in-humans
#18
Luis Arturo Ruvalcaba Castellón, Martha Isolina García Amador, Roberto Enrique Díaz González, Montoya Sarmiento Jorge Eduardo, César Díaz-García, Niclas Kvarnström, Mats Bränström
This paper aimed to describe the basic aspects of uterine transplant (UTx) research in humans, including preliminary experiences in rodents and domestic species. Studies in rats, domestic species, and non-human primates validated and optimized the UTx procedure in terms of its surgical aspects, immunosuppression, rejection diagnosis, peculiarities of pregnancy in immunosuppressed patients, and patients with special uterine conditions. In animal species, the first live birth from UTx was achieved in a syngeneic mouse model in 2003...
June 1, 2017: JBRA Assisted Reproduction
https://www.readbyqxmd.com/read/28534508/utx-promotes-hormonally-responsive-breast-carcinogenesis-through-feed-forward-transcription-regulation-with-estrogen-receptor
#19
G Xie, X Liu, Y Zhang, W Li, S Liu, Z Chen, B Xu, J Yang, L He, Z Zhang, T Jin, X Yi, L Sun, Y Shang, J Liang
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis...
September 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28529687/histone-demethylases-utx-and-jmjd3-are-required-for-nkt-cell-development-in-mice
#20
Daniel Northrup, Ryoji Yagi, Kairong Cui, William R Proctor, Chaochen Wang, Katarzyna Placek, Lance R Pohl, Rongfu Wang, Kai Ge, Jinfang Zhu, Keji Zhao
BACKGROUND: Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. RESULTS: We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected...
2017: Cell & Bioscience
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