scholarly journals Mixed lineage leukaemia histone methylases 1 collaborate with ERα to regulate HOXA10 expression in AML

2014 ◽  
Vol 34 (6) ◽  
Author(s):  
Jie Yao ◽  
Li-Chao Fang ◽  
Zai-Lin Yang ◽  
Hui Huang ◽  
Yan Li ◽  
...  
Keyword(s):  
Mixed Lineage Leukaemia

We find that E2 could elevate HOXA10 expression. We examine HOXA10 regulated by MLL1 with an epigenetic way. MLL1 bind to HOXA10 promoter through formatting complex with mainly ERα.

scholarly journals MLL1 minimal catalytic complex is a dynamic conformational ensemble susceptible to pharmacological allosteric disruption

2018 ◽  
Author(s):  
Lilia Kaustov ◽  
Alexander Lemak ◽  
Hong Wu ◽  
Marco Faini ◽  
Scott Houliston ◽  
...  
Keyword(s):  
Hybrid Methods ◽  
Structural Basis ◽  
Epigenetic Mark ◽  
Conformational Ensemble ◽  
Interaction Sites ◽  
Catalytic Function ◽  
Individual Interaction ◽  
Mixed Lineage Leukaemia ◽  
Repeat Domain ◽  
Histone H3k4

ABSTRACTHistone H3K4 methylation is an epigenetic mark associated with actively transcribed genes. This modification is catalyzed by the mixed lineage leukaemia (MLL) family of histone methyltransferases including MLL1, MLL2, MLL3, MLL4, SET1A and SET1B. Catalytic activity of MLL proteins is dependent on interactions with additional conserved proteins but the structural basis for subunit assembly and the mechanism of regulation is not well understood. We used a hybrid methods approach to study the assembly and biochemical function of the minimally active MLL1 complex (MLL1, WDR5 and RbBP5). A combination of small angle X-ray scattering (SAXS), cross-linking mass spectrometry (XL-MS), NMR spectroscopy, and computational modeling were used to generate a dynamic ensemble model in which subunits are assembled via multiple weak interaction sites. We identified a new interaction site between the MLL1 SET domain and the WD40 repeat domain of RbBP5, and demonstrate the susceptibility of the catalytic function of the complex to disruption of individual interaction sites.

scholarly journals The MLL1 trimeric catalytic complex is a dynamic conformational ensemble stabilized by multiple weak interactions

2019 ◽  
Author(s):  
Lilia Kaustov ◽  
Alexander Lemak ◽  
Hong Wu ◽  
Marco Faini ◽  
Lixin Fan ◽  
...  
Keyword(s):  
Hybrid Methods ◽  
Weak Interactions ◽  
Structural Basis ◽  
Resonance Spectroscopy ◽  
Epigenetic Mark ◽  
Conformational Ensemble ◽  
Interaction Sites ◽  
Catalytic Function ◽  
Mixed Lineage Leukaemia ◽  
Histone H3k4

Abstract Histone H3K4 methylation is an epigenetic mark associated with actively transcribed genes. This modification is catalyzed by the mixed lineage leukaemia (MLL) family of histone methyltransferases including MLL1, MLL2, MLL3, MLL4, SET1A and SET1B. The catalytic activity of this family is dependent on interactions with additional conserved proteins, but the structural basis for subunit assembly and the mechanism of regulation is not well understood. We used a hybrid methods approach to study the assembly and biochemical function of the minimally active MLL1 complex (MLL1, WDR5 and RbBP5). A combination of small angle X-ray scattering, cross-linking mass spectrometry, nuclear magnetic resonance spectroscopy and computational modeling were used to generate a dynamic ensemble model in which subunits are assembled via multiple weak interaction sites. We identified a new interaction site between the MLL1 SET domain and the WD40 β-propeller domain of RbBP5, and demonstrate the susceptibility of the catalytic function of the complex to disruption of individual interaction sites.

scholarly journals Subcellular localization of EEN/endophilin A2, a fusion partner gene in leukaemia

2004 ◽  
Vol 383 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Ngai CHEUNG ◽  
Chi Wai SO ◽  
Judy W. P. YAM ◽  
C. K. C. SO ◽  
Randy Y. C. POON ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Fusion Partner ◽  
Nucleocytoplasmic Shuttling ◽  
Cellular Functions ◽  
Protein Levels ◽  
Mixed Lineage Leukaemia ◽  
Partner Gene ◽  
M Phase ◽  
Endocytic Vesicles

EEN (extra eleven nineteen), also known as EA2 (endophilin A2), a fusion partner of the MLL (mixed-lineage leukaemia) gene in human acute leukaemia, is a member of the endophilin A family, involved in the formation of endocytic vesicles. We present evidence to show that EEN/EA2 is localized predominantly in nuclei of various cell lines of haemopoietic, fibroblast and epithelial origin, in contrast with its reported cytoplasmic localization in neurons and osteoclasts, and that EEN/EA2 exhibits nucleocytoplasmic shuttling. During the cell cycle, EEN/EA2 shows dynamic localization: it is perichromosomal in prometaphase, co-localizes with the bipolar spindle in metaphase and anaphase and redistributes to the midzone and midbody in telophase. This pattern of distribution coincides with changes in protein levels of EEN/EA2, with the highest levels being observed in G2/M-phase. Our results suggest that distinct subcellular localization of the endophilin A family members probably underpins their diverse cellular functions and indicates a role for EEN/EA2 in the cell cycle.

Absence of global hypomethylation in promoter hypermethylated Mixed Lineage Leukaemia-rearranged infant acute lymphoblastic leukaemia

2013 ◽  
Vol 49 (1) ◽  
pp. 175-184 ◽  
Author(s):  
Dominique J.P.M. Stumpel ◽  
Pauline Schneider ◽  
Eddy H.J. van Roon ◽  
Rob Pieters ◽  
Ronald W. Stam
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Global Hypomethylation ◽  
Mixed Lineage Leukaemia

Glucocorticoid sensitisation in Mixed Lineage Leukaemia-rearranged acute lymphoblastic leukaemia by the pan-BCL-2 family inhibitors gossypol and AT-101

2014 ◽  
Vol 50 (9) ◽  
pp. 1665-1674 ◽  
Author(s):  
Jill A.P. Spijkers-Hagelstein ◽  
Pauline Schneider ◽  
Sandra Mimoso Pinhanços ◽  
Patricia Garrido Castro ◽  
Rob Pieters ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Mixed Lineage Leukaemia

scholarly journals Therapy-related, mixed-lineage leukaemia translocation-positive, monoblastic myeloid sarcoma of the uterus

2006 ◽  
Vol 60 (5) ◽  
pp. 562-564 ◽  
Author(s):  
V. Pullarkat ◽  
L. Veliz ◽  
K. Chang ◽  
A. Mohrbacher ◽  
A. L. Teotico ◽  
...  
Keyword(s):  
Myeloid Sarcoma ◽  
Mixed Lineage Leukaemia

scholarly journals Protein network study of human AF4 reveals its central role in RNA Pol II-mediated transcription and in phosphorylation-dependent regulatory mechanisms

2011 ◽  
Vol 438 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Gabriella Esposito ◽  
Armando Cevenini ◽  
Alessandro Cuomo ◽  
Francesca de Falco ◽  
Dario Sabbatino ◽  
...  
Keyword(s):  
Fragile X ◽  
Regulatory Mechanisms ◽  
Transcriptional Elongation ◽  
Interacting Proteins ◽  
Cyclin Dependent Kinase ◽  
Multiprotein Complex ◽  
Physiological Mechanisms ◽  
Rna Pol Ii ◽  
Proteomic Approach ◽  
Mixed Lineage Leukaemia

AF4 belongs to a family of proteins implicated in childhood lymphoblastic leukaemia, FRAXE (Fragile X E site) mental retardation and ataxia. AF4 is a transcriptional activator that is involved in transcriptional elongation. Although AF4 has been implicated in MLL (mixed-lineage leukaemia)-related leukaemogenesis, AF4-dependent physiological mechanisms have not been clearly defined. Proteins that interact with AF4 may also play important roles in mediating oncogenesis, and are potential targets for novel therapies. Using a functional proteomic approach involving tandem MS and bioinformatics, we identified 51 AF4-interacting proteins of various Gene Ontology categories. Approximately 60% participate in transcription regulatory mechanisms, including the Mediator complex in eukaryotic cells. In the present paper we report one of the first extensive proteomic studies aimed at elucidating AF4 protein cross-talk. Moreover, we found that the AF4 residues Thr220 and Ser212 are phosphorylated, which suggests that AF4 function depends on phosphorylation mechanisms. We also mapped the AF4-interaction site with CDK9 (cyclin-dependent kinase 9), which is a direct interactor crucial for the function and regulation of the protein. The findings of the present study significantly expand the number of putative members of the multiprotein complex formed by AF4, which is instrumental in promoting the transcription/elongation of specific genes in human cells.

scholarly journals ZF-CxxC domain-containing proteins, CpG islands and the chromatin connection

2013 ◽  
Vol 41 (3) ◽  
pp. 727-740 ◽  
Author(s):  
Hannah K. Long ◽  
Neil P. Blackledge ◽  
Robert J. Klose
Keyword(s):  
Transcriptional Repression ◽  
Cpg Islands ◽  
Chromatin Modification ◽  
Lysine Methylation ◽  
Histone Tails ◽  
Cpg Dinucleotides ◽  
Methylated Dna ◽  
Chemically Modified ◽  
Mixed Lineage Leukaemia ◽  
Lysine Demethylase

Vertebrate DNA can be chemically modified by methylation of the 5 position of the cytosine base in the context of CpG dinucleotides. This modification creates a binding site for MBD (methyl-CpG-binding domain) proteins which target chromatin-modifying activities that are thought to contribute to transcriptional repression and maintain heterochromatic regions of the genome. In contrast with DNA methylation, which is found broadly across vertebrate genomes, non-methylated DNA is concentrated in regions known as CGIs (CpG islands). Recently, a family of proteins which encode a ZF-CxxC (zinc finger-CxxC) domain have been shown to specifically recognize non-methylated DNA and recruit chromatin-modifying activities to CGI elements. For example, CFP1 (CxxC finger protein 1), MLL (mixed lineage leukaemia protein), KDM (lysine demethylase) 2A and KDM2B regulate lysine methylation on histone tails, whereas TET (ten-eleven translocation) 1 and TET3 hydroxylate methylated cytosine bases. In the present review, we discuss the most recent advances in our understanding of how ZF-CxxC domain-containing proteins recognize non-methylated DNA and describe their role in chromatin modification at CGIs.

scholarly journals Photoperiod Influences Growth and mll (Mixed-Lineage Leukaemia) Expression in Atlantic Cod

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e36908 ◽  
Author(s):  
Kazue Nagasawa ◽  
Alessia Giannetto ◽  
Jorge M. O. Fernandes
Keyword(s):  
Atlantic Cod ◽  
Mixed Lineage Leukaemia
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