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https://www.readbyqxmd.com/read/28976802/the-mixed-lineage-leukemia-4-mll4-methyltransferase-complex-is-involved-in-transforming-growth-factor-beta-tgf-%C3%AE-activated-gene-transcription
#1
Roy Baas, Hetty A A M van Teeffelen, Sjoerd J D Tjalsma, H Th Marc Timmers
Sma and Mad related (SMAD)-mediated Transforming Growth Factor β (TGF-β) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-β-activated SMAD signaling...
October 4, 2017: Transcription
https://www.readbyqxmd.com/read/28967912/histone-h3k4-monomethylation-catalyzed-by-trr-and-mammalian-compass-like-proteins-at-enhancers-is-dispensable-for-development-and-viability
#2
Ryan Rickels, Hans-Martin Herz, Christie C Sze, Kaixiang Cao, Marc A Morgan, Clayton K Collings, Maria Gause, Yoh-Hei Takahashi, Lu Wang, Emily J Rendleman, Stacy A Marshall, Annika Krueger, Elizabeth T Bartom, Andrea Piunti, Edwin R Smith, Nebiyu A Abshiru, Neil L Kelleher, Dale Dorsett, Ali Shilatifard
Histone H3 lysine 4 monomethylation (H3K4me1) is an evolutionarily conserved feature of enhancer chromatin catalyzed by the COMPASS-like methyltransferase family, which includes Trr in Drosophila melanogaster and MLL3 (encoded by KMT2C) and MLL4 (encoded by KMT2D) in mammals. Here we demonstrate that Drosophila embryos expressing catalytically deficient Trr eclose and develop to productive adulthood. Parallel experiments with a trr allele that augments enzyme product specificity show that conversion of H3K4me1 at enhancers to H3K4me2 and H3K4me3 is also compatible with life and results in minimal changes in gene expression...
November 2017: Nature Genetics
https://www.readbyqxmd.com/read/28927028/decreased-expression-of-the-long-non-coding-rna-mllt4-antisense-rna-1-is-a-potential-biomarker-and-an-indicator-of-a-poor-prognosis-for-gastric-cancer
#3
Yuexing Lai, Ping Xu, Jie Liu, Qinghua Li, Dabin Ren, Jun Zhang, Jing Wang
In recent years, the identification of long non-coding RNAs (lncRNAs) led to the analysis of their characteristics in cancer biology. However, the expression of lncRNAs in cancer and their clinical significance remain unclear. In the present study, an investigation of lncRNAs that may be involved in the regulation of metastasis using microarray and polymerase chain reaction analyses resulted in the identification of MLLT4 antisense RNA 1 (MLLT4-AS1) as a significantly downregulated lncRNA in gastric cancer tissue compared with normal adjacent tissue (P=0...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28829449/mll4-keeps-foxp3-in-the-loop
#4
Dong-Mei Zhao, Hai-Hui Xue
No abstract text is available yet for this article.
August 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28805231/the-histone-methyltransferase-mixed-lineage-leukemia-mll-3-may-play-a-potential-role-on-clinical-dilated-cardiomyopathy
#5
Ding-Sheng Jiang, Xin Yi, Rui Li, Yun-Shu Su, Jing Wang, Min-Lai Chen, Li-Gang Liu, Min Hu, Cai Cheng, Ping Zheng, Xue-Hai Zhu, Xiang Wei
Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM). While the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families on DCM are unclear. To this end, twelve normal and fifteen DCM heart samples were included in the present study. A murine cardiac remodelling model was induced by transverse aortic constriction (TAC). Real-time PCR was performed to detect the expression levels of MLL families in the mouse and human left ventricles...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28759003/mll4-prepares-the-enhancer-landscape-for-foxp3-induction-via-chromatin-looping
#6
Katarzyna Placek, Gangqing Hu, Kairong Cui, Dunfang Zhang, Yi Ding, Ji-Eun Lee, Younghoon Jang, Chaochen Wang, Joanne Elizabeth Konkel, Jiuzhou Song, Chengyu Liu, Kai Ge, Wanjun Chen, Keji Zhao
MLL4 is an essential subunit of the histone H3 Lys4 (H3K4)-methylation complexes. We found that MLL4 deficiency compromised the development of regulatory T cells (Treg cells) and resulted in a substantial decrease in monomethylated H3K4 (H3K4me1) and chromatin interaction at putative gene enhancers, a considerable portion of which were not direct targets of MLL4 but were enhancers that interacted with MLL4-bound sites. The decrease in H3K4me1 and chromatin interaction at the enhancers not bound by MLL4 correlated with MLL4 binding at distant interacting regions...
September 2017: Nature Immunology
https://www.readbyqxmd.com/read/28732206/a-utx-mll4-p300-transcriptional-regulatory-network-coordinately-shapes-active-enhancer-landscapes-for-eliciting-transcription
#7
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/28669924/histone-h3-lysine-4-methyltransferase-kmt2d
#8
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/28483418/mll3-and-mll4-facilitate-enhancer-rna-synthesis-and-transcription-from-promoters-independently-of-h3k4-monomethylation
#9
Kristel M Dorighi, Tomek Swigut, Telmo Henriques, Natarajan V Bhanu, Benjamin S Scruggs, Nataliya Nady, Christopher D Still, Benjamin A Garcia, Karen Adelman, Joanna Wysocka
Monomethylation of histone H3 at lysine 4 (H3K4me1) and acetylation of histone H3 at lysine 27 (H3K27ac) are correlated with transcriptionally engaged enhancer elements, but the functional impact of these modifications on enhancer activity is not well understood. Here we used CRISPR/Cas9 genome editing to separate catalytic activity-dependent and independent functions of Mll3 (Kmt2c) and Mll4 (Kmt2d, Mll2), the major enhancer H3K4 monomethyltransferases. Loss of H3K4me1 from enhancers in Mll3/4 catalytically deficient cells causes partial reduction of H3K27ac, but has surprisingly minor effects on transcription from either enhancers or promoters...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28461566/correction-utx-and-mll4-coordinately-regulate-transcriptional-programs-for-cell-proliferation-and-invasiveness-in-breast-cancer-cells
#10
(no author information available yet)
No abstract text is available yet for this article.
May 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28398509/mll3-mll4-are-required-for-cbp-p300-binding-on-enhancers-and-super-enhancer-formation-in-brown-adipogenesis
#11
Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge
Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes in cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ), coactivator MED1, RNA polymerase II, as well as epigenome (H3K4me1/2/3, H3K9me2, H3K27me3, H3K36me3, H3K27ac), transcriptome and chromatin opening during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT)...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28375985/distinct-functions-of-histone-h3-lysine-4-methyltransferases-in-normal-and-malignant-hematopoiesis
#12
REVIEW
Weiwei Yang, Patricia Ernst
PURPOSE OF REVIEW: Histone H3, lysine 4 (H3K4) methylation is one chromatin modification that defines distinct regulatory states of euchromatin. Mammals express six main histone methyltransferase (HMT) enzymes that modify H3K4 by monomethylation, dimethylation or trimethylation. Recent studies examine roles of some of these HMTs and their cofactors in hematopoiesis and leukemia. We discuss these emerging studies together with prior embryonic stem data, revealing how these enzymes function...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28361674/batvi-fast-sensitive-and-accurate-detection-of-virus-integrations
#13
Chandana Tennakoon, Wing Kin Sung
BACKGROUND: The study of virus integrations in human genome is important since virus integrations were shown to be associated with diseases. In the literature, few methods have been proposed that predict virus integrations using next generation sequencing datasets. Although they work, they are slow and are not very sensitive. RESULTS AND DISCUSSION: This paper introduces a new method BatVI to predict viral integrations. Our method uses a fast screening method to filter out chimeric reads containing possible viral integrations...
March 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#14
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
June 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28124401/brca1-alterations-with-additional-defects-in-dna-damage-response-genes-may-confer-chemoresistance-to-brca-like-breast-cancers-treated-with-neoadjuvant-chemotherapy
#15
Mamoru Takada, Shigenori Nagai, Masayuki Haruta, Ryuichi P Sugino, Katsunori Tozuka, Hiroyuki Takei, Fumie Ohkubo, Kenichi Inoue, Masafumi Kurosumi, Masaru Miyazaki, Aiko Sato-Otsubo, Yusuke Sato, Seishi Ogawa, Yasuhiko Kaneko
The BRCA-like phenotype is a feature that some sporadic breast cancers share with those occurring in BRCA1 or BRCA2 mutation carriers. As tumors with the phenotype have defects in the DNA damage response pathway, which may increase sensitivity to drugs such as DNA cross-linking agents and PARP inhibitors, a method to identify this phenotype is important. The prediction of chemoresistance, which frequently develops in these tumors, is also crucial for improving therapy. We examined genomic aberrations and BRCA1 promoter methylation in tumors of 73 breast cancer (20 HR-/HER2- and 53 HR+/HER2-) patients, who received neoadjuvant chemotherapy with anthracycline, cyclophosphamide, and taxane, using SNP array CGH and quantitative PCR...
May 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28067305/gomisin-n-inhibits-adipogenesis-and-prevents-high-fat-diet-induced-obesity
#16
Min-Kyung Jang, Ye-Rang Yun, Ji-Hyun Kim, Mi-Hee Park, Myeong Ho Jung
Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28013028/h3k4-methyltransferase-activity-is-required-for-mll4-protein-stability
#17
Younghoon Jang, Chaochen Wang, Lenan Zhuang, Chengyu Liu, Kai Ge
Transcriptional enhancers play a key role in cell type-specific gene expression and cell fate transition. Enhancers are marked by histone H3K4 mono- and di-methylation (H3K4me1/2). The tumor suppressor MLL4 (KMT2D) is a major enhancer H3K4 mono- and di-methyltransferase with a partial functional redundancy with MLL3 (KMT2C). However, the functional role of MLL4 enzymatic activity remains elusive. To address this issue, we have generated MLL4 enzyme-dead knock-in (KI) embryonic stem (ES) cells and mice, which carry Y5477A/Y5523A/Y5563A mutations in the enzymatic SET domain of the MLL4 protein...
June 30, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27992417/mutations-in-the-histone-methyltransferase-gene-kmt2b-cause-complex-early-onset-dystonia
#18
Esther Meyer, Keren J Carss, Julia Rankin, John M E Nichols, Detelina Grozeva, Agnel P Joseph, Niccolo E Mencacci, Apostolos Papandreou, Joanne Ng, Serena Barral, Adeline Ngoh, Hilla Ben-Pazi, Michel A Willemsen, David Arkadir, Angela Barnicoat, Hagai Bergman, Sanjay Bhate, Amber Boys, Niklas Darin, Nicola Foulds, Nicholas Gutowski, Alison Hills, Henry Houlden, Jane A Hurst, Zvi Israel, Margaret Kaminska, Patricia Limousin, Daniel Lumsden, Shane McKee, Shibalik Misra, Shekeeb S Mohammed, Vasiliki Nakou, Joost Nicolai, Magnus Nilsson, Hardev Pall, Kathryn J Peall, Gregory B Peters, Prab Prabhakar, Miriam S Reuter, Patrick Rump, Reeval Segel, Margje Sinnema, Martin Smith, Peter Turnpenny, Susan M White, Dagmar Wieczorek, Sarah Wiethoff, Brian T Wilson, Gidon Winter, Christopher Wragg, Simon Pope, Simon J H Heales, Deborah Morrogh, Alan Pittman, Lucinda J Carr, Belen Perez-Dueñas, Jean-Pierre Lin, Andre Reis, William A Gahl, Camilo Toro, Kailash P Bhatia, Nicholas W Wood, Erik-Jan Kamsteeg, Wui K Chong, Paul Gissen, Maya Topf, Russell C Dale, Jonathan R Chubb, F Lucy Raymond, Manju A Kurian
Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings...
February 2017: Nature Genetics
https://www.readbyqxmd.com/read/27932267/human-pre-pik3c2b-an-intronic-cis-element-with-dual-function-of-activation-and-repression
#19
Jayant Maini, Mohsen Ghasemi, Deepti Yandhuri, Suman S Thakur, Vani Brahmachari
The Polycomb/Trithorax Responsive Elements (PRE/TREs) are the cis-regulatory sequences that interact with both repressive (PcG) as well as activating (TrxG) complexes. However, most of the mammalian PREs are demonstrated to interact with the repressive polycomb (PcG) complexes only. We have carried out an unbiased search for proteins interacting with human PRE-PIK3C2B (hPRE-PIK3C2B) based on DNA affinity purification followed by mass spectrometry and identified MLL, MLL4 and WDR87 among other proteins in three biological replicates in HEK, U87 and HeLa cell lines...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27806304/critical-roles-of-the-histone-methyltransferase-mll4-kmt2d-in-murine-hepatic-steatosis-directed-by-abl1-and-ppar%C3%AE-2
#20
Dae-Hwan Kim, Janghyun Kim, Ji-Sun Kwon, Jaspreet Sandhu, Peter Tontonoz, Soo-Kyung Lee, Seunghee Lee, Jae W Lee
The pathophysiologic continuum of non-alcoholic fatty liver disease begins with steatosis. Despite recent advances in our understanding of the gene regulatory program directing steatosis, how it is orchestrated at the chromatin level is unclear. PPARγ2 is a hepatic steatotic transcription factor induced by overnutrition. Here, we report that the histone H3 lysine 4 methyltransferase MLL4/KMT2D directs overnutrition-induced murine steatosis via its coactivator function for PPARγ2. We demonstrate that overnutrition facilitates the recruitment of MLL4 to steatotic target genes of PPARγ2 and their transactivation via H3 lysine 4 methylation because PPARγ2 phosphorylated by overnutrition-activated ABL1 kinase shows enhanced interaction with MLL4...
November 1, 2016: Cell Reports
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