scholarly journals The autoimmune regulator PHD finger binds to non‐methylated histone H3K4 to activate gene expression

EMBO Reports ◽  
2008 ◽  
Vol 9 (4) ◽  
pp. 370-376 ◽  
Author(s):  
Tõnis Org ◽  
Francesca Chignola ◽  
Csaba Hetényi ◽  
Massimiliano Gaetani ◽  
Ana Rebane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phd Finger ◽  
Autoimmune Regulator ◽  
Histone H3k4 ◽  
Activate Gene

scholarly journals The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression

EMBO Reports ◽  
2008 ◽  
Vol 9 (4) ◽  
pp. 370-376 ◽  
Author(s):  
Tõnis Org ◽  
Francesca Chignola ◽  
Csaba Hetényi ◽  
Massimiliano Gaetani ◽  
Ana Rebane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phd Finger ◽  
Autoimmune Regulator ◽  
Histone H3k4 ◽  
Activate Gene

The MLL PHD Fingers of MLL Block MLL Fusion Protein Mediated Transformation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 976-976
Author(s):  
Andrew G. Muntean ◽  
Jay L. Hess
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Fusion Protein ◽  
Fusion Proteins ◽  
Hox Genes ◽  
Bone Marrow Cells ◽  
Nurd Complex ◽  
Inhibition Of Proliferation ◽  
Phd Finger ◽  
Histone H3k4

Abstract Mixed Lineage Leukemia (MLL) is a histone H3K4 methyltransferase that is rearranged in both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). MLL is required for the maintenance of Hox gene expression. Deregulation of Hox genes by MLL fusion proteins, which fuse MLL in frame to one of over 50 different translocation partners, is critical for transformation. In these translocations, the DNMT homology (CXXC) domain is always included, but the set of adjacent plant homeodomains (PHD), which includes four PHD fingers and a bromodomain, is invariably excluded. PHD fingers have recently been described to bind tri-methylated histone H3K4 and others report PHD domains binding transcriptional co-repressors, such as Mi-2a of the NuRD complex. However, the role of the PHD fingers in MLL is not well understood. To determine the function of the PHD fingers in MLL, we performed bone marrow transduction and colony assays with the MLL fusion protein MLL-AF9, engineered to contain the PHD domain region (MLL-PHD-AF9). These experiments showed that inclusion of the PHD fingers inhibited immortalization as shown by the absence of compact colonies in methylcellulose replating assays and inhibition of proliferation in liquid cultures. Initial experiments with PHD finger deletions to map the inhibiting activity suggest inclusion of any PHD fingers beyond the first PHD finger, results in inhibition of transformation. To monitor the transcriptional activity of the retrovirally infected bone marrow cells, total RNA was isolated from cells harvested after the second replating, when significant differences were seen in colony morphology and size. Consistent with the transformation inhibition, Hoxa9 gene expression was found to be significantly repressed with respect to expression detected in transformed MLL-AF9 cells as determined by qPCR. To confirm this effect is directly due to the MLL fusion proteins, we performed luciferase assays with an MLL responsive myc E-box luciferase construct in MLL −/− MEFs. We found a specific and robust activation of the reporter in the presence of MLL-AF9, which was severely compromised by the inclusion of the PHD fingers. Together, these results suggest the PHD fingers act as transcriptional repressors that inhibit transformation. Our results provide an explanation for the finding that translocations including the coding region for C terminal PHD fingers do not occur in human leukemias and suggest that this region is also involved in the regulation of wild type MLL. We are currently studying the mechanisms of transcriptional repression mediated by the PHD fingers by isolating interacting proteins and assessing their effect on transcription and transformation.

scholarly journals Unmodified Histone H3K4 and DNA-Dependent Protein Kinase Recruit Autoimmune Regulator to Target Genes

2012 ◽  
Vol 32 (8) ◽  
pp. 1354-1362 ◽  
Author(s):  
K. Zumer ◽  
A. K. Low ◽  
H. Jiang ◽  
K. Saksela ◽  
B. M. Peterlin
Keyword(s):  
Protein Kinase ◽  
Target Genes ◽  
Dependent Protein Kinase ◽  
Autoimmune Regulator ◽  
Dependent Protein ◽  
Histone H3k4

scholarly journals The PHD finger of Arabidopsis SIZ1 recognizes trimethylated histone H3K4 mediating SIZ1 function and abiotic stress response

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Kenji Miura ◽  
Na Renhu ◽  
Takuya Suzaki
Keyword(s):  
Stress Responses ◽  
Abiotic And Biotic Stress ◽  
Abiotic Stress Response ◽  
Phd Finger ◽  
Transcriptional Suppression ◽  
Plant Homeodomain ◽  
Histone H3k4 ◽  
Cold Sensitive ◽  
Sumo E3 Ligase ◽  
Aba Hypersensitivity

AbstractArabidopsis SIZ1 encodes a SUMO E3 ligase to regulate abiotic and biotic stress responses. Among SIZ1 or mammalian PIAS orthologs, plant SIZ1 proteins contain the plant homeodomain (PHD) finger, a C4HC3 zinc finger. Here, we investigated the importance of PHD of Arabidopsis SIZ1. The ProSIZ1::SIZ1(ΔPHD):GFP was unable to complement growth retardation, ABA hypersensitivity, and the cold-sensitive phenotype of the siz1 mutant, but ProSIZ1::SIZ1:GFP could. Substitution of C162S in the PHD finger was unable to complement the siz1 mutation. Tri-methylated histone H3K4 (H3K4me3) was recognized by PHD, not by PHD(C162S). WRKY70 was up-regulated in the siz1-2 mutant and H3K4me3 accumulated at high levels in the WRKY70 promoter. PHD interacts with ATX, which mediates methylation of histone, probably leading to suppression of ATX’s function. These results suggest that the PHD finger of SIZ1 is important for recognition of the histone code and is required for SIZ1 function and transcriptional suppression.

scholarly journals xB elements strongly activate gene expression in non-lymphoid cells and function synergistically with NF1 elements

1989 ◽  
Vol 17 (20) ◽  
pp. 8197-8206 ◽  
Author(s):  
Lothar Henninghausen ◽  
Priscilla A. Furth ◽  
Chirstoph W. Pittius
Keyword(s):  
Gene Expression ◽  
Lymphoid Cells ◽  
And Function ◽  
Activate Gene

scholarly journals Correlation analysis of VHL and Jade-1 gene expression in human renal cell carcinoma

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 226-230 ◽  
Author(s):  
Wu Xiao-fen ◽  
Chen Ting ◽  
Li Jie ◽  
Ma Deng-yang ◽  
Zhu Qing-feng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Grade ◽  
Human Renal Cell Carcinoma ◽  
Clinical Prognosis ◽  
Phd Finger ◽  
Von Hippel Lindau ◽  
Normal Tissues

AbstractObjectiveThe aim of this study was to investigate the correlation of von Hippel-Lindau tumor suppressor (VHL) mRNA expression and jade family PHD finger 1 (Jade-1) gene expression in patients with renal cell carcinoma (RCC). Another aim of this study was to analyze the relationship of these two genes with clinicalpathological features of the RCC patients. Methods: A total of 75 RCC patients who received surgically therapy in our hospital were included. All patients had complete pathological data. The expression of VHL/Jade-1 was determined by real-time polymerase chain reaction (RT-PCR). Results: VHL and Jade-1 were both obviously downregulated in RCC tissues than that of the matched normal tissues, and both negatively correlated with tumor size as well as tumor grade. And we found a fine association of VHL gene expression with Jade-1. Conclusion: VHL/Jade-1 exhibited significantly decreased expression in RCC tissues and was closely related to the clinical prognosis of patients. The finding of VHL expression positively correlated with Jade-1 expression shed light and provided crucial evidence on the connection of VHL protein with Wnt/b-catenin pathway.

scholarly journals Enhancer RNAs: transcriptional regulators and workmates of NamiRNAs in myogenesis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Emmanuel Odame ◽  
Yuan Chen ◽  
Shuailong Zheng ◽  
Dinghui Dai ◽  
Bismark Kyei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Transcriptional Regulators ◽  
Chromatin Looping ◽  
Functional Differences ◽  
Non Coding Rnas ◽  
And Function ◽  
Activate Gene ◽  
Promoter Interaction

AbstractmiRNAs are well known to be gene repressors. A newly identified class of miRNAs termed nuclear activating miRNAs (NamiRNAs), transcribed from miRNA loci that exhibit enhancer features, promote gene expression via binding to the promoter and enhancer marker regions of the target genes. Meanwhile, activated enhancers produce endogenous non-coding RNAs (named enhancer RNAs, eRNAs) to activate gene expression. During chromatin looping, transcribed eRNAs interact with NamiRNAs through enhancer-promoter interaction to perform similar functions. Here, we review the functional differences and similarities between eRNAs and NamiRNAs in myogenesis and disease. We also propose models demonstrating their mutual mechanism and function. We conclude that eRNAs are active molecules, transcriptional regulators, and partners of NamiRNAs, rather than mere RNAs produced during enhancer activation.

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