CHD8 Is an ATP-Dependent Chromatin Remodeling Factor That Regulates β-Catenin Target Genes

ABSTRACT ATP-dependent chromatin remodeling by the CHD family of proteins plays an important role in the regulation of gene transcription. Here we report that full-length CHD8 interacts directly with β-catenin and that CHD8 is also recruited specifically to the promoter regions of several β-catenin-responsive genes. Our results indicate that CHD8 negatively regulates β-catenin-targeted gene expression, since short hairpin RNA against CHD8 results in the activation of several β-catenin target genes. This regulation is also conserved through evolution; RNA interference against kismet, the apparent Drosophila ortholog of CHD8, results in a similar activation of β-catenin target genes. We also report the first demonstration of chromatin remodeling activity for a member of the CHD6-9 family of proteins, suggesting that CHD8 functions in transcription through the ATP-dependent modulation of chromatin structure.

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BRG1-Mediated Chromatin Remodeling Regulates Differentiation and Gene Expression of T Helper Cells

Molecular and Cellular Biology ◽

10.1128/mcb.00835-08 ◽

2008 ◽

Vol 28 (24) ◽

pp. 7274-7285 ◽

Cited By ~ 51

Author(s):

Andrea L. Wurster ◽

Michael J. Pazin

Keyword(s):

Gene Expression ◽

Cell Fate ◽

Chromatin Remodeling ◽

Chromatin Structure ◽

Target Genes ◽

T Helper Cell ◽

T Helper ◽

T Helper 2 ◽

Th2 Cytokine ◽

Th2 Differentiation

ABSTRACT During T helper cell differentiation, distinct programs of gene expression play a key role in defining the immune response to an environmental challenge. How chromatin remodeling events at the associated cytokine loci control differentiation is not known. We found that the ATP-dependent remodeling enzyme subunit BRG1 was required for T helper 2 (Th2) differentiation and Th2 cytokine transcription. BRG1 binding to cytokine genes was regulated by the extent of differentiation, the extent of activation, and cell fate. BRG1 was required for some features of the chromatin structure in target genes (DNase I hypersensitivity and histone acetylation), suggesting that BRG1 remodeling activity was directly responsible for changes in gene expression. NFAT and STAT6 activity were required for BRG1 recruitment to the Th2 locus control region, and STAT6 associated with BRG1 in a differentiation-inducible manner, suggesting direct recruitment of BRG1 to the bound loci. Together, these findings suggest BRG1 interprets differentiation signals and plays a causal role in gene regulation, chromatin structure, and cell fate.

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Effective reduction of the interleukin-1β transcript in osteoarthritis-prone guinea pig chondrocytes via short hairpin RNA mediated RNA interference influences gene expression of mediators implicated in disease pathogenesis

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2011.09.004 ◽

2011 ◽

Vol 19 (12) ◽

pp. 1449-1457 ◽

Cited By ~ 26

Author(s):

K.S. Santangelo ◽

A.L. Bertone

Keyword(s):

Gene Expression ◽

Rna Interference ◽

Guinea Pig ◽

Short Hairpin Rna ◽

Interleukin 1Β ◽

Disease Pathogenesis ◽

Hairpin Rna ◽

Effective Reduction ◽

Short Hairpin

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Faculty Opinions recommendation of Short hairpin RNA-expressing bacteria elicit RNA interference in mammals.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1032558.489061 ◽

2006 ◽

Author(s):

Vitaly Citovsky

Keyword(s):

Rna Interference ◽

Short Hairpin Rna ◽

Hairpin Rna ◽

Short Hairpin

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Stable Suppression of Gene Expression in Murine Embryonic Stem Cells by RNAi Directed from DNA Vector-Based Short Hairpin RNA

Stem Cells ◽

10.1634/stemcells.22-1-93 ◽

2004 ◽

Vol 22 (1) ◽

pp. 93-99 ◽

Cited By ~ 15

Author(s):

Fu-Chou Tang ◽

Guo-Liang Meng ◽

Hong-Bo Yang ◽

Cheng-Jian Li ◽

Yan Shi ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Short Hairpin Rna ◽

Hairpin Rna ◽

Murine Embryonic Stem Cells ◽

Short Hairpin ◽

Dna Vector ◽

Suppression Of Gene Expression

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Suppression of bovine viral diarrhea virus replication by single and dual short hairpin RNA-mediated RNA interference

Research in Veterinary Science ◽

10.1016/j.rvsc.2011.08.004 ◽

2012 ◽

Vol 93 (1) ◽

pp. 544-548 ◽

Cited By ~ 6

Author(s):

Wei Ni ◽

Shengwei Hu ◽

Jun Qiao ◽

Yuan Yu ◽

Dawei Wang ◽

...

Keyword(s):

Rna Interference ◽

Virus Replication ◽

Bovine Viral Diarrhea Virus ◽

Short Hairpin Rna ◽

Bovine Viral Diarrhea ◽

Hairpin Rna ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Short Hairpin ◽

Viral Diarrhea Virus

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Multiplexed, Targeted Gene Expression Profiling and Genetic Analysis on Electronic Microarrays

Clinical Chemistry ◽

10.1093/clinchem/48.11.1873 ◽

2002 ◽

Vol 48 (11) ◽

pp. 1873-1882 ◽

Cited By ~ 18

Author(s):

Elaine M Weidenhammer ◽

Brenda F Kahl ◽

Ling Wang ◽

Larry Wang ◽

Melanie Duhon ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Target Genes ◽

Mrna Targets ◽

Amplification Method ◽

Polymorphism Detection ◽

Targeted Gene Expression ◽

Electronic Microarray ◽

Electronic Field

Abstract Background: Electronic microarrays comprise independent microelectrode test sites that can be electronically biased positive or negative, or left neutral, to move and concentrate charged molecules such as DNA and RNA to one or more test sites. We developed a protocol for multiplexed gene expression profiling of mRNA targets that uses electronic field-facilitated hybridization on electronic microarrays. Methods: A multiplexed, T7 RNA polymerase-mediated amplification method was used for expression profiling of target mRNAs from total cellular RNA; targets were detected by hybridization to sequence-specific capture oligonucleotides on electronic microarrays. Activation of individual test sites on the electronic microarray was used to target hybridization to designated subsets of sites and allow comparisons of target concentrations in different samples. We used multiplexed amplification and electronic field-facilitated hybridization to analyze expression of a model set of 10 target genes in the U937 cell line during lipopolysaccharide-mediated differentiation. Performance of multiple genetic analyses (single-nucleotide polymorphism detection, gene expression profiling, and splicing isoform detection) on a single electronic microarray was demonstrated using the ApoE and ApoER2 genes as a model system. Results: Targets were detected after a 2-min hybridization reaction. With noncomplementary capture probes, no signal was detectable. Twofold changes in target concentration were detectable throughout the (∼64-fold) range of concentrations tested. Levels of 10 targets were analyzed side by side across seven time points. By confining electronic activation to subsets of test sites, polymorphism detection, expression profiling, and splicing isoform analysis were performed on a single electronic microarray. Conclusions: Microelectronic array technology provides specific target detection and quantification with advantages over currently available methodologies for targeted gene expression profiling and combinatorial genomics testing.

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Lentiviral Vector-Mediated Delivery of Short Hairpin RNA Results in Persistent Knockdown of Gene Expression in Mouse Brain

Human Gene Therapy ◽

10.1089/104303403322611809 ◽

2003 ◽

Vol 14 (18) ◽

pp. 1799-1807 ◽

Cited By ~ 76

Author(s):

Chris Van den Haute ◽

Kristel Eggermont ◽

Bart Nuttin ◽

Zeger Debyser ◽

Veerle Baekelandt

Keyword(s):

Gene Expression ◽

Mouse Brain ◽

Lentiviral Vector ◽

Short Hairpin Rna ◽

Hairpin Rna ◽

Short Hairpin

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High doses of siRNAs induce eri-1 and adar-1 gene expression and reduce the efficiency of RNA interference in the mouse

Biochemical Journal ◽

10.1042/bj20050647 ◽

2005 ◽

Vol 390 (3) ◽

pp. 675-679 ◽

Cited By ~ 37

Author(s):

Jie Hong ◽

Zhikang Qian ◽

Shuiyuan Shen ◽

Taishan Min ◽

Chang Tan ◽

...

Keyword(s):

Gene Expression ◽

Hepatitis B Virus ◽

Rna Interference ◽

Hepatitis B ◽

Adenosine Deaminase ◽

Surface Antigen ◽

Target Genes ◽

Virus Surface ◽

Virus Surface Antigen ◽

B Virus

RNAi (RNA interference) is a gene-silencing mechanism that is conserved in evolution from worm to human and has been a powerful tool for gene functional research. It has been clear that the RNAi effect triggered by endogenous or exogenous siRNAs (small interfering RNAs) is transient and dose-dependent. However, there is little information on the regulation of RNAi. Recently, some proteins that regulate the RNA-silencing machinery have been identified. We have observed in previous work that the expression of target genes rebounds after being suppressed for a period of time by siRNAs. In the present study, we used secretory hepatitis B virus surface antigen gene as a reporter and compared its expression level in cell culture and mice challenged by different doses of siRNAs. A quicker and higher rebound of gene expression was observed in mice tail-vein-injected with higher doses of siRNA, and the rebound was associated with an increase in the mRNA level of meri-1 (mouse enhanced RNAi) and adar-1 (adenosine deaminase acting on RNA) genes encoding an exonuclease and RNA-specific adenosine deaminase respectively. Down-regulation of meri-1 by RNAi enhanced the sensitivity and efficiency of siRNA in inhibiting the expression of hepatitis B virus surface antigen. These results indicate that RNAi machinery may be under negative regulation, through the induction of a series of genes coding for destabilizing enzymes, by siRNAs introduced into the cell, and also suggest that a suitable amount of siRNA should be used for research or therapeutic applications.

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