ライフサイエンスコーパス: BRM

1 BRM encodes the catalytic ATPase required for chromatin

2 BRM interacts with two ankyrin repeat proteins that are

3 BRM is developed using Java and other open-source techno

4 BRM is developed using Java and other open-source techno

5 BRM provides the ability to mine complex data for identi

6 BRM v2.3 has the capability to query predicted miRNA tar

7 BRM was identified as a transcriptional activator of Hox

8 BRM, a key SWI/SNF complex subunit and a putative tumor

9 BRM, sample data sets and a user manual can be downloade

10 BRM-specific complexes are present only on the repressed

11 7%), SAIDs in 29 (7.4%), IMT in 149 (38.0%), BRMs in 56 (14.3%), and none (N = 14).

12 ddress this question, we sequenced BRM in 10 BRM/BRG1-deficient cancer cell lines and found that BRM

13 E2F binding-deficient basic region mutant 2 (BRM-2) carrying the Ile294Ala and Arg297Ala substitution

14 we report the characterization of BAP111, a BRM-associated protein that contains a high mobility gro

15 modifying antirheumatic drug before use of a BRM).

16 ility of biologic response modifying agents (BRMs) by mandating that health plans that provide covera

17 e pathway regulates both BRM acetylation and BRM silencing as MAP kinase pathway inhibitors both indu

18 Furthermore, we show that AN3 and BRM genetically interact.

19 Lastly, we demonstrate that both BAF57 and BRM are required for the proliferation of AR-dependent p

20 t the SWI/SNF ATPase subunits cell, BRG1 and BRM (BRG1/BRM), are lost in approximately 30% of human n

21 t provides supportive evidence that BRG1 and BRM act as tumor suppressor proteins and implicates a ro

22 long terminal repeat), we show that BRG1 and BRM are recruited to the MMTV promoter in a hormone-depe

23 Thus, BRG1 and BRM are silenced by different mechanisms, and it may be

24 netic and mechanistic basis for the BRG1 and BRM chromatin-remodeling complexes in regulating gene ex

25 Thus, BRG1 and BRM complexes may direct distinct cellular processes by

26 f tumors show a concomitant loss of BRG1 and BRM expression.

27 Because BRG1 and BRM function as mutually exclusive catalytic subunits of

28 show concomitant down-regulation of BRG1 and BRM in six human tumor cell lines.

29 The recruitment of BRG1 and BRM resulted in chromatin remodeling and decondensation

30 BRG1 and BRM were required for the viability of VECs but not othe

31 BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin

32 e of two highly homologous ATPases, BRG1 and BRM, yet little is known about their specialized functio

33 chromatin-remodeling complex called BRG1 and BRM.

34 subunits including the two ATPases BRG1 and BRM.

35 nges in the relative importance of BRG1- and BRM-catalyzed SWI/SNF complexes during the development o

36 Furthermore, CHD9 and BRM were required for GR occupancy and chromatin remodel

37 tively inhibits GR interaction with CHD9 and BRM, thereby blocking chromatin remodeling and robust GR

38 AMPK2 phoshorylation site impaired KU70 and BRM recruitment to DSB sites.

39 ded direct evidence that BRG1, BRG1-K-R, and BRM chromatin-remodeling complexes have distinct kinetic

40 y, the core ATPase subunits, BRG/SMARCA4 and BRM/SMARCA2, are functionally distinct and may contribut

41 ved Brm complex core subunits, SNR1/SNF5 and BRM/SNF2-SWI2, on target gene regulation.

42 A widespread distribution of SNR1 and BRM on the salivary gland polytene chromosomes showed th

43 5, GRF3, COL5, and ARR4, and both SWP73B and BRM occupy the HEC1 promoter.

44 SYD and BRM act as trithorax proteins, and the requirement for S

45 ax proteins, and the requirement for SYD and BRM in flower patterning can be overcome by partial loss

46 We show that UTX and BRM are physically associated with CBP in vivo and that

47 UTX and BRM bind directly to conserved zinc fingers of CBP, sugg

48 We propose that direct binding of UTX and BRM to CBP and their modulation of H3K27ac play an impor

49 ncluded RCTs that compared the safety of any BRMs used in RA patients with placebo and/or any traditi

50 roader biological interest, in areas such as BRM and Polycomb group function and dysfunction, transcr

51 f REF6 results in decreased BRM occupancy at BRM-REF6 co-targets.

52 Downregulation of the single ATPase, BRM, in SK-MEL5 cells inhibited expression of both diffe

53 ing enzymes that contain SNF2 family ATPases BRM (Brahma) or BRG1 (Brahma Related Gene 1) and that co

54 owered by either of two alternative ATPases, BRM or BRG1.

55 an be either of two closely related ATPases, BRM or BRG1, with the potential that the choice of alter

56 Designed in collaboration with biologists, BRM simplifies mundane analysis tasks of merging microar

57 pression, these HDAC inhibitors also blocked BRM function when present.

58 that the promoter is a direct target of both BRM- and BRG1-containing complexes.

59 man tumor types and that loss of one or both BRM alleles potentiated tumor development in mice.

60 protein (MAP) kinase pathway regulates both BRM acetylation and BRM silencing as MAP kinase pathway

61 Brahma (BRM) and Brahma-related gene 1 (BRG1) are the ATP-depend

62 Brahma (BRM) is a novel anticancer gene, which is frequently ina

63 remodeling ATPases SPLAYED (SYD) and BRAHMA (BRM) are redundantly required for flower patterning and

64 F-type chromatin remodelers, such as BRAHMA (BRM), and H3K27 demethylases both have active roles in r

65 WI2/SNF2 chromatin remodeling ATPase BRAHMA (BRM) causes ABA hypersensitivity during postgermination

66 SWI/SNF chromatin-remodeling ATPase BRAHMA (BRM) modulates response to ABA by preventing premature a

67 and the chromatin-remodeling ATPase Brahma (BRM).

68 complexes formed around the ATPases BRAHMA (BRM) or SPLAYED.

69 rabidopsis thaliana SWI/SNF ATPases, BRAHMA (BRM) and SPLAYED (SYD), are viable, facilitating investi

70 SWI/SNF chromatin remodeling enzyme Brahma (BRM).

71 rahma-related gene-1 (BRG1) or human brahma (BRM), the ATPase subunits of two distinct SWI/SNF enzyme

72 xpress dominant negative versions of Brahma (BRM) and Brahma-related gene 1 (BRG1), the ATPase subuni

73 ATPases as their catalytic subunit: brahma (BRM, also known as SMARCA2) and brahma-related gene 1 (B

74 e of two paralogous ATPase subunits, Brahma (BRM) or BRM-related gene 1 (BRG1), which we previously f

75 bind to itself and it interacts with Brahma (BRM), an SWI2-SNF2 homolog, with which it is associated

76 (iii) chromatin remodeling, including BRG1, BRM, hSNF2H, BAF155, mSin3a, and histone deacetylase 2.

77 of the 60-kD structural subunit BAF60 (BRG1/BRM-associated factor 60), of which BAF60c is essential

78 SNF ATPase subunits cell, BRG1 and BRM (BRG1/BRM), are lost in approximately 30% of human non-small l

79 e-stimulated macrophages, the catalytic BRG1/BRM subunits of the SWI/SNF class of ATP-dependent nucle

80 Here, we show that the BRG1/BRM-associated factor (BAF) chromatin remodeling complex

81 estored BRM expression in each of these BRG1/BRM-deficient cancer cell lines, indicating that epigene

82 st that hSNF5 loss is not equivalent to BRG1/BRM loss in human tumor cell lines.

83 Moreover, patients with BRG1/BRM-negative carcinomas, independent of stage, have a st

84 in survival compared with patients with BRG1/BRM.

85 We show that BRG1and BRM associate with different promoters during cellular p

86 e-deficient forms of BRG1 (BRG1-K-R) or BRM (BRM-K-R) inhibited the remodeling of local and higher or

87 Regulation of Antennapedia by BRM and OSA proteins requires sequences 5' to the P2 pro

88 nhibitors both induced BRM as well as caused BRM deacetylation.

89 catalytic subunits of the SWI/SNF complexes, BRM, the mammalian ortholog of SWI2/SNF2 in yeast and br

90 apid phosphorylation-based switch to control BRM activity; this property could be potentially harness

91 Loss of REF6 results in decreased BRM occupancy at BRM-REF6 co-targets.

92 Since the E2F binding-deficient BRM-2 mutant interacted with E2F-1 but failed to activat

93 Our results offer a rationale to develop BRM-ATPase inhibitors as a strategy to treat BRG1/SMARCA

94 onfidence intervals were calculated for each BRM.

95 transcription factors (TFs) linked to either BRM (GATA3) or HDAC9 (MEF2D) expression.

96 oncurrently, the chromatin-remodeling factor BRM is replaced by BRG1 and histones are hyperacetylated

97 ate that the BAP111 subunit is important for BRM complex function in vivo.

98 We propose a role for BRM in the balance between growth or stress responses.

99 The results reveal an unexpected role for BRM-specific complexes.

100 A switch from BRM to BRG1 on the alkaline phosphatase promoter marks t

101 However, assorted tissues from BRM null/BRG1-positive mice lack CD44 expression, sugges

102 Unlike many anticancer genes, BRM is not mutated, but rather epigenetically silenced.

103 teracts with BRG1 and its functional homolog BRM in mammalian cells.

104 nding protein 9 (CHD9) and Brahma homologue (BRM, a product of the SMARCA2 gene) are required for GC-

105 Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity fo

106 ial sarcoma, is known to interact with human BRM (hBRM), thus providing a link between chromatin remo

107 This screen identified BRM/SMARCA2, a DNA-dependent ATPase of the mammalian SWI

108 To determine if BRM physically interacts with other trithorax group prot

109 and HDAC9 were greatly overexpressed only in BRM-negative cell lines indicating that HDAC9 may be a g

110 que N-terminal domain that is not present in BRM.

111 alcin, become constitutively up-regulated in BRM-depleted cells.

112 rentially regulated (p<0.05) gene targets in BRM indicates that nicotine exposure disrupts genes invo

113 The miRNA workflow in BRM allows for efficient processing of multiple miRNA an

114 and found that KAT6A, KAT6B and KAT7 induce BRM expression, whereas KAT2B and KAT8 induce its acetyl

115 and/or MEF2D downregulated HDAC9 and induced BRM.

116 s MAP kinase pathway inhibitors both induced BRM as well as caused BRM deacetylation.

117 ression of BRM-dependent genes and inhibited BRM-dependent growth across a wide range of BRM-deficien

118 MOR thus joins BRM and Snf5-related 1 (SNR1), two known Drosophila SWI-

119 The Bioinformatics Resource Manager (BRM) is a software environment that provides the user wi

120 The Bioinformatics Resource Manager (BRM) v2.3 is a software environment for data management,

121 ivo but does not affect assembly of the 2-MD BRM complex.

122 rapy [IMT]), or biologic response modifiers (BRMs) was assessed.

123 the infusion of biologic response modifiers (BRMs), including antileukocyte antibodies and lipids.

124 o are receiving biologic response modifiers (BRMs).

125 act with BRM and post-translationally modify BRM by phosphorylation/dephosphorylation.

126 Although dominant negative BRM and BRG1 inhibited expression of every muscle-specif

127 the presence or absence of dominant negative BRM or BRG1, MyoD was able to activate expression of p21

128 Expression of the dominant-negative BRM protein caused peripheral nervous system defects, ho

129 osphorylation of BRM restores the ability of BRM to repress ABA response.

130 NA repair by suppressing the accumulation of BRM, a catalytic subunit of the SWI/SNF complex, at DSB

131 ion, and PP2CA-mediated dephosphorylation of BRM restores the ability of BRM to repress ABA response.

132 s was seen with BRG1 depletion, depletion of BRM caused accelerated progression to the differentiatio

133 Depletion of BRM in BRG1-deficient cancer cells leads to a cell cycle

134 Dissociation of BRM-containing SWI/SNF depends on p300, and association

135 oth compounds led to robust re-expression of BRM, induced downstream expression of BRM-dependent gene

136 ion of BRM, induced downstream expression of BRM-dependent genes and inhibited BRM-dependent growth a

137 The strategy relies upon inhibition of BRM/SMARCA2, another catalytic SWI/SNF subunit with a BR

138 ralogous SWI/SNF subunits with low levels of BRM, BAF170, and ARID1B.

139 Moreover, loss of BRM activity led to destabilization of a nucleosome like

140 is a major mechanism underlying the loss of BRM expression.

141 of these genes is not compromised by loss of BRM function.

142 ke other tumor suppressor genes, the loss of BRM has been shown to be a reversible epigenetic change,

143 gest that SnRK2-dependent phosphorylation of BRM leads to its inhibition, and PP2CA-mediated dephosph

144 re induction, but the concurrent presence of BRM-specific complexes overrides their activation functi

145 BRM-dependent growth across a wide range of BRM-deficient cancer cell lines of different origins.

146 ) domains and facilitates the recruitment of BRM.

147 Reduction of BRM function dramatically reduces the association of RNA

148 horylation sites in the C-terminal region of BRM at SnRK2 target sites that are evolutionarily conser

149 which underlie the epigenetic regulation of BRM.

150 NA interference (RNAi)-mediated silencing of BRM suppressed the growth of BRG1-deficient cancer cells

151 We also found that the suppression of BRM occurs in a broad range of human tumor types and tha

152 which underlie the epigenetic suppression of BRM.

153 The bromodomain-containing C terminus of BRM binds to the CBP PHD finger, enhances PHD binding to

154 The use of BRMs among patients with RA included in RCTs of at least

155 complex thus correlates with a dependence on BRM for gene activity.

156 elective dependency of BRG1-mutant tumors on BRM in vivo.

157 ions of SWI/SNF complexes containing BRG1 or BRM are not completely interchangeable.

158 nducibly express mutant forms of the BRG1 or BRM ATPases that are unable to bind and hydrolyze ATP.

159 that expression of dominant negative BRG1 or BRM inhibited the induction of muscle-specific gene expr

160 rmined that expression of the mutant BRG1 or BRM proteins impaired the ability of cells to activate t

161 SNF complexes composed of either the BRG1 or BRM subunit promote expression of distinct and overlappi

162 posed of one of two related ATPases, BRG1 or BRM, and 9-12-associated factors (BAFs).

163 cells and observed downregulation of BRG1 or BRM, but not concomitant loss of both ATPases.

164 essing dominant negative versions of BRG1 or BRM-based SWI/SNF enzymes.

165 atin remodeling complexes containing BRG1 or BRM.

166 wo highly conserved ATPase subunits: BRG1 or BRM.

167 paralogous ATPase subunits, Brahma (BRM) or BRM-related gene 1 (BRG1), which we previously found are

168 in cell lines that lack functional p300, or BRM and Brg-1.

169 ATPase-deficient forms of BRG1 (BRG1-K-R) or BRM (BRM-K-R) inhibited the remodeling of local and high

170 mall fraction of all genes depends on SYD or BRM for expression, indicating that these SWI/SNF ATPase

171 iated systemic disease may respond to IMT or BRMs.

172 ed for several days, and during this period, BRM activity was detected.

173 Finally, the phosphomimetic BRM(S1760D S1762D) mutant displays ABA hypersensitivity.

174 Our findings position BRM as an attractive therapeutic target for BRG1 mutated

175 human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckle

176 Our studies revealed that reduced BRM expression and/or activity drives the malignant beha

177 possible to clinically target and reexpress BRM in a number of tumor types, potentially impacting tu

178 ow which specific proteins, if any, regulate BRM, we sought to identify the proteins, which underlie

179 HDAC, we found that HDAC3 and HDAC9 regulate BRM expression, whereas HDAC2 controls its acetylation.

180 of compounds that could effectively restore BRM expression and function.

181 Despite their ability to restore BRM expression, these HDAC inhibitors also blocked BRM f

182 stone deacetylase (HDAC) inhibitors restored BRM expression in each of these BRG1/BRM-deficient cance

183 are effective at pharmacologically restoring BRM and thereby inhibit cancer cell growth.

184 Consistently, we could show that restoring BRM levels normalized the malignant behavior of transfor

185 s, revealing that SNR1 functions to restrict BRM-dependent nucleosome remodeling activities downstrea

186 rect; chromatin immunoprecipitation revealed BRM binding to the ABI5 locus.

187 mplex (HDAC) inhibitors are known to reverse BRM silencing, but they also inactivate it via acetylati

188 To address this question, we sequenced BRM in 10 BRM/BRG1-deficient cancer cell lines and found

189 ction of a 'core' subunit to block or shield BRM (SWI2/SNF2) activity in specific cells.

190 ive catalytic subunits, SMARCA4 and SMARCA2 (BRM).

191 table components, even though the SWI2/SNF2 (BRM, BRG1, hBRM) ATPase subunit alone is partially suffi

192 WI/SNF chromatic remodeling complex subunit, BRM, is a potentially viable and novel therapeutic appro

193 Drosophila Brahma (SWI/SNF) complex subunits BRM and SNR1 are highly conserved with direct counterpar

194 By transient transfection, we found that BRM can restore RB-mediated cell cycle arrest, induce ex

195 1-deficient cancer cell lines and found that BRM was devoid of abrogating mutations.

196 wever, after their removal, we observed that BRM expression remained elevated for several days, and d

197 l RNAi study conducted in vivo revealed that BRM depletion suppressed the growth of BRG1-deficient tu

198 Prior studies showed that BRM resides at target loci in the ABA pathway in the pre

199 These findings suggest that BRM plays a role in chromatin remodeling that is distinc

200 e mice lack CD44 expression, suggesting that BRM-containing SWI/SNF complexes regulate expression of

201 Genetic evidence suggests that BRM acts downstream of SnRK2.2/2.3 kinases, and biochemi

202 The BRM complex contains at least seven major polypeptides.

203 The BRM complex is associated with nearly all transcriptiona

204 The BRM complex is even more highly related to the human BRG

205 xate group (0.77%; 95% CI, 0.65%-0.92%), the BRM monotherapy group (0.64%; 95% CI, 0.42%-0.95%), and

206 0 and CBP histone acetyltransferases and the BRM and Brg-1 chromatin remodeling complexes are recruit

207 hat it may modulate interactions between the BRM complex and chromatin.

208 mammalian cells, these complexes contain the BRM and BRG1 helicase-like proteins that are thought to

209 steoblasts, SWI/SNF complexes containing the BRM ATPase repress osteoblast-specific genes to maintain

210 Consistent with these findings, the BRM protein is expressed at relatively high levels in nu

211 ibility and show specific enrichment for the BRM remodeler.

212 he first year of therapy was very low in the BRM plus methotrexate group (0.77%; 95% CI, 0.65%-0.92%)

213 our screens: genes encoding subunits of the BRM complex (brm, moira, and osa), other proteins direct

214 isingly, the majority of the subunits of the BRM complex are not encoded by trithorax group genes.

215 Four of the subunits of the BRM complex are related to subunits of the yeast chromat

216 To clarify the role of the BRM complex in the transcription of other genes, we exam

217 hat the chromatin remodeling activity of the BRM complex plays a general role in facilitating transcr

218 The distribution of the BRM complex thus correlates with a dependence on BRM for

219 e targeting, function, and regulation of the BRM complex, we screened for mutations that genetically

220 rget genes by regulating the activity of the BRM complex.

221 equired for the assembly or stability of the BRM complex.

222 eins, the deletion of the bromodomain of the BRM protein has no discernible phenotype.

223 served lysine in the ATP-binding site of the BRM protein with an arginine.

224 te the functions of conserved regions of the BRM protein.

225 Genomic targets of the BRM remodeler overlap significantly with FGT1 targets.

226 ransferases p300, CBP, PCAF, and GCN5 or the BRM and Brg-1 chromatin remodeling complexes did not dim

227 er trithorax group proteins, we purified the BRM complex from Drosophila embryos and analyzed its sub

228 demonstrates its key role in recruiting the BRM chromatin remodeler.

229 propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes.

230 11 protein in embryos is associated with the BRM complex.

231 heat shock loci, are not associated with the BRM complex; transcription of these genes is not comprom

232 Therefore, BRM may be consistently down-regulated with BRG1 during

233 ing, no mutations were found in any of these BRM-regulating HDACs, HATs or TFs.

234 nown, may be required for optimal binding to BRM.

235 nally, the abi5 null mutant was epistatic to BRM in postgermination growth arrest.

236 In this study, we report recent updates to BRM for miRNA data analysis and cross-species comparison

237 cancer cell lines, the mechanisms underlying BRM silencing are not known.

238 Here we use BRM to show that developmental exposure of zebrafish to

239 We show typical workflows for using BRM to integrate experimental zebrafish miRNA and mRNA m

240 ly associated with CBP in vivo and that UTX, BRM, and CBP colocalize genome-wide on Polycomb response

241 development and embryonic survival, whereas BRM is dispensable.

242 We tested whether BRM could affect aberrant cellular functions attributed

243 e analyses showed that REF6 colocalizes with BRM at many genomic sites with the CTCTGYTY motif.

244 pathway components physically interact with BRM and post-translationally modify BRM by phosphorylati

245 y through protein-protein interactions, with BRM in the case of SYT, and with Polycomb group represso

246 Successful treatment with BRMs was associated with diffuse or nodular scleritis wi