;PMID: 9642136 ;source_file_1781.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..53] = [t:0..53] ;1)sentence:[e:59..120] = [t:59..120] ;2)section:[e:124..158] = [t:124..158] ;3)section:[e:162..271] = [t:162..271] ;4)sentence:[e:275..418] = [t:275..418] ;5)sentence:[e:419..537] = [t:419..537] ;6)sentence:[e:538..816] = [t:538..816] ;7)sentence:[e:818..988] = [t:818..988] ;8)sentence:[e:989..1123] = [t:989..1123] ;9)sentence:[e:1125..1327] = [t:1125..1327] ;10)sentence:[e:1328..1439] = [t:1328..1439] ;11)sentence:[e:1440..1603] = [t:1440..1603] ;12)sentence:[e:1604..1683] = [t:1604..1683] ;13)sentence:[e:1684..1873] = [t:1684..1873] ;14)sentence:[e:1874..1946] = [t:1874..1946] ;15)sentence:[e:1947..2078] = [t:1947..2078] ;16)section:[e:2079..2109] = [t:2079..2109] ;17)section:[e:2113..2157] = [t:2113..2157] ;section 0 Span:0..53 ;Biochem Biophys Res Commun. 1998 Jun 18;247(2):383-6. (SEC (FRAG (NNP:[0..7] Biochem) (NNP:[8..15] Biophys) (NNP:[16..19] Res) (NNP:[20..26] Commun) (.:[26..27] .) (CD:[28..32] 1998) (NNP:[33..36] Jun) (CD:[37..44] 18;247-LRB-) (CD:[44..45] 2) (-RRB-:[45..46] -RRB-) (::[46..47] :) (CD:[47..50] 383) (HYPH:[50..51] -) (CD:[51..53] 6.))) ;sentence 1 Span:59..120 ;Silencing of CYP1A1 expression in rabbits by DNA methylation. ;[72..78]:cyp450:"CYP1A1" ;[104..107]:substance:"DNA" (SENT (NP-HLN (NP (NN:[59..68] Silencing)) (PP (IN:[69..71] of) (NP (NN:[72..78] CYP1A1) (NN:[79..89] expression))) (PP-LOC (IN:[90..92] in) (NP (NNS:[93..100] rabbits))) (PP (IN:[101..103] by) (NP (NN:[104..107] DNA) (NN:[108..119] methylation))) (.:[119..120] .))) ;section 2 Span:124..158 ;Takahashi Y, Suzuki C, Kamataki T. (SEC (FRAG (NNP:[124..133] Takahashi) (NNP:[134..135] Y) (,:[135..136] ,) (NNP:[137..143] Suzuki) (NNP:[144..145] C) (,:[145..146] ,) (NNP:[147..155] Kamataki) (NNP:[156..158] T.))) ;section 3 Span:162..271 ;Faculty of Pharmaceutical Sciences, Hokkaido University, N12W6, Kita-ku, ;Hokkaido, Sapporo, 060-0812, Japan. (SEC (FRAG (IN:[162..169] Faculty) (IN:[170..172] of) (NNP:[173..187] Pharmaceutical) (NNPS:[188..196] Sciences) (,:[196..197] ,) (NNP:[198..206] Hokkaido) (NNP:[207..217] University) (,:[217..218] ,) (NNP:[219..224] N12W6) (,:[224..225] ,) (NNP:[226..233] Kita-ku) (,:[233..234] ,) (NNP:[236..244] Hokkaido) (,:[244..245] ,) (NNP:[246..253] Sapporo) (,:[253..254] ,) (CD:[255..258] 060) (CD:[258..263] -0812) (,:[263..264] ,) (NNP:[265..270] Japan) (.:[270..271] .))) ;sentence 4 Span:275..418 ;Unlike most experimental animals, treatment of adult rabbits with ;3-methylcholanthrene (MC) does not induce the expression of the CYP1A1 gene. ;[342..362]:substance:"3-methylcholanthrene" ;[364..366]:substance:"MC" (SENT (S (PP (IN:[275..281] Unlike) (NP (JJS:[282..286] most) (JJ:[287..299] experimental) (NNS:[300..307] animals))) (,:[307..308] ,) (NP-SBJ (NP (NN:[309..318] treatment)) (PP (IN:[319..321] of) (NP (JJ:[322..327] adult) (NNS:[328..335] rabbits))) (PP-CLR (IN:[336..340] with) (NP (NP (NN:[342..362] 3-methylcholanthrene)) (NP (-LRB-:[363..364] -LRB-) (NN:[364..366] MC) (-RRB-:[366..367] -RRB-))))) (VP (VBZ:[368..372] does) (RB:[373..376] not) (VP (VB:[377..383] induce) (NP (NP (DT:[384..387] the) (NN:[388..398] expression)) (PP (IN:[399..401] of) (NP (DT:[402..405] the) (NN:[406..412] CYP1A1) (NN:[413..417] gene)))))) (.:[417..418] .))) ;sentence 5 Span:419..537 ;In this study, we show that DNA methylation plays one of the key roles in ;the suppression of CYP1A1 gene expression. ;[448..451]:substance:"DNA" (SENT (S (PP-LOC (IN:[419..421] In) (NP (DT:[423..427] this) (NN:[428..433] study))) (,:[433..434] ,) (NP-SBJ (PRP:[435..437] we)) (VP (VBP:[438..442] show) (SBAR (IN:[443..447] that) (S (NP-SBJ (NN:[448..451] DNA) (NN:[452..463] methylation)) (VP (VBZ:[464..469] plays) (NP (NP (CD:[470..473] one)) (PP (IN:[474..476] of) (NP (NP (DT:[477..480] the) (JJ:[481..484] key) (NNS:[485..490] roles)) (PP (IN:[491..493] in) (NP (NP (DT:[494..497] the) (NN:[499..510] suppression)) (PP (IN:[511..513] of) (NP (NN:[514..520] CYP1A1) (NN:[521..525] gene) (NN:[526..536] expression)))))))))))) (.:[536..537] .))) ;sentence 6 Span:538..816 ;S1 nuclease protection assay showed that the induction of CYP1A1 mRNA by MC ;occurred in rabbit kidney RK13 cells but not in rabbit lung R9ab cells, ;while aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (Arnt) ;mRNAs were expressed in both cells at similar levels. ;[597..608]:substance:"CYP1A1 mRNA" ;[612..614]:substance:"MC" ;[694..719]:substance:"aryl hydrocarbon receptor" ;[721..724]:substance:"AhR" ;[730..755]:substance:"AhR nuclear translocator" ;[757..761]:substance:"Arnt" ;[763..768]:substance:"mRNAs" (SENT (S (NP-SBJ (NML (NN:[538..540] S1) (NN:[541..549] nuclease) (NN:[550..560] protection)) (NN:[561..566] assay)) (VP (VBD:[567..573] showed) (SBAR (IN:[574..578] that) (S (NP-SBJ (NP (DT:[580..583] the) (NN:[584..593] induction)) (PP (IN:[594..596] of) (NP (NN:[597..603] CYP1A1) (NN:[604..608] mRNA))) (PP (IN:[609..611] by) (NP (NN:[612..614] MC)))) (VP (VP (VBD:[615..623] occurred) (PP-LOC=3 (IN:[624..626] in) (NP (NN:[627..633] rabbit) (NN:[634..640] kidney) (NN:[641..645] RK13) (NNS:[646..651] cells)))) (CC:[652..655] but) (RB:[656..659] not) (VP (PP-LOC=3 (IN:[661..663] in) (NP (NN:[664..670] rabbit) (NN:[671..675] lung) (NN:[676..680] R9ab) (NNS:[681..686] cells)))) (,:[686..687] ,) (SBAR-ADV (IN:[688..693] while) (S (NP-SBJ-4 (NP (NML (NML (NML (NN:[694..698] aryl) (NN:[699..710] hydrocarbon)) (NN:[711..719] receptor)) (NML (-LRB-:[720..721] -LRB-) (NN:[721..724] AhR) (-RRB-:[724..725] -RRB-))) (NML-1 (-NONE-:[725..725] *P*))) (CC:[726..729] and) (NP (NML (NML (NN:[730..733] AhR) (JJ:[734..741] nuclear) (NN:[743..755] translocator)) (NML (-LRB-:[756..757] -LRB-) (NN:[757..761] Arnt) (-RRB-:[761..762] -RRB-))) (NML-1 (NNS:[763..768] mRNAs)))) (VP (VBD:[769..773] were) (VP (VBN:[774..783] expressed) (NP-4 (-NONE-:[783..783] *)) (PP-LOC (IN:[784..786] in) (NP (DT:[787..791] both) (NNS:[792..797] cells))) (PP (IN:[798..800] at) (NP (JJ:[801..808] similar) (NNS:[809..815] levels))))))))))) (.:[815..816] .))) ;sentence 7 Span:818..988 ;Interestingly, the treatment of R9ab cells with a DNA demethylating agent, ;5-aza-2'-deoxycitidine, resulted in the induction of the expression of the ;CYP1A1 gene by MC. ;[868..871]:substance:"DNA" ;[886..891]:substance:"agent" ;[894..916]:substance:"5-aza-2'-deoxycitidine" ;[985..987]:substance:"MC" (SENT (S (ADVP (RB:[818..831] Interestingly)) (,:[831..832] ,) (NP-SBJ (NP (DT:[833..836] the) (NN:[837..846] treatment)) (PP (IN:[847..849] of) (NP (NN:[850..854] R9ab) (NNS:[855..860] cells))) (PP (IN:[861..865] with) (NP (NP (DT:[866..867] a) (ADJP (NN:[868..871] DNA) (VBG:[872..885] demethylating)) (NN:[886..891] agent)) (,:[891..892] ,) (NP (NN:[894..916] 5-aza-2'-deoxycitidine))))) (,:[916..917] ,) (VP (VBD:[918..926] resulted) (PP-CLR (IN:[927..929] in) (NP (NP (DT:[930..933] the) (NN:[934..943] induction)) (PP (IN:[944..946] of) (NP (NP (DT:[947..950] the) (NN:[951..961] expression)) (PP (IN:[962..964] of) (NP (DT:[965..968] the) (NN:[970..976] CYP1A1) (NN:[977..981] gene))) (PP (IN:[982..984] by) (NP (NN:[985..987] MC)))))))) (.:[987..988] .))) ;sentence 8 Span:989..1123 ;The results indicate that DNA methylation is one of the factors involved in ;the loss of the MC-induced expression of the CYP1A1 gene. ;[1015..1018]:substance:"DNA" ;[1082..1084]:substance:"MC" (SENT (S (NP-SBJ (DT:[989..992] The) (NNS:[993..1000] results)) (VP (VBP:[1001..1009] indicate) (SBAR (IN:[1010..1014] that) (S (NP-SBJ (NN:[1015..1018] DNA) (NN:[1019..1030] methylation)) (VP (VBZ:[1031..1033] is) (NP-PRD (NP (CD:[1034..1037] one)) (PP (IN:[1038..1040] of) (NP (NP (DT:[1041..1044] the) (NNS:[1046..1053] factors)) (VP (VBN:[1054..1062] involved) (NP (-NONE-:[1062..1062] *)) (PP-CLR (IN:[1063..1065] in) (NP (NP (DT:[1066..1069] the) (NN:[1070..1074] loss)) (PP (IN:[1075..1077] of) (NP (NP (DT:[1078..1081] the) (ADJP (NN:[1082..1084] MC) (HYPH:[1084..1085] -) (VBN:[1085..1092] induced)) (NN:[1093..1103] expression)) (PP (IN:[1104..1106] of) (NP (DT:[1107..1110] the) (NN:[1111..1117] CYP1A1) (NN:[1118..1122] gene))))))))))))))) (.:[1122..1123] .))) ;sentence 9 Span:1125..1327 ;Thus, it seemed that the binding of the AhR/Arnt complex to the ;xenobiotic-responsive element (XRE) was inhibited by the hypermethylation of ;CpG dinucleotides within an XRE core sequence (5'-CGTG-3'). ;[1165..1168]:substance:"AhR" ;[1169..1173]:substance:"Arnt" ;[1190..1219]:substance:"xenobiotic-responsive element" ;[1221..1224]:substance:"XRE" ;[1267..1285]:substance:"CpG dinucleotides" ;[1296..1299]:substance:"XRE" (SENT (S (ADVP (RB:[1125..1129] Thus)) (,:[1129..1130] ,) (NP-SBJ (PRP:[1131..1133] it)) (VP (VBD:[1134..1140] seemed) (SBAR (IN:[1141..1145] that) (S (NP-SBJ-1 (NP (DT:[1146..1149] the) (NN:[1150..1157] binding)) (PP (IN:[1158..1160] of) (NP (DT:[1161..1164] the) (NML (NN:[1165..1168] AhR) (SYM:[1168..1169] /) (NN:[1169..1173] Arnt)) (NN:[1174..1181] complex))) (PP (TO:[1182..1184] to) (NP (NP (DT:[1185..1188] the) (ADJP (JJ:[1190..1200] xenobiotic) (HYPH:[1200..1201] -) (JJ:[1201..1211] responsive)) (NN:[1212..1219] element)) (NP (-LRB-:[1220..1221] -LRB-) (NN:[1221..1224] XRE) (-RRB-:[1224..1225] -RRB-))))) (VP (VBD:[1226..1229] was) (VP (VBN:[1230..1239] inhibited) (NP-1 (-NONE-:[1239..1239] *)) (PP (IN:[1240..1242] by) (NP-LGS (NP (DT:[1243..1246] the) (NN:[1247..1263] hypermethylation)) (PP (IN:[1264..1266] of) (NP (NN:[1267..1270] CpG) (NNS:[1272..1285] dinucleotides))) (PP (IN:[1286..1292] within) (NP (NP (DT:[1293..1295] an) (NN:[1296..1299] XRE) (NN:[1300..1304] core) (NN:[1305..1313] sequence)) (NP (-LRB-:[1314..1315] -LRB-) (NN:[1315..1325] 5'-CGTG-3') (-RRB-:[1325..1326] -RRB-))))))))))) (.:[1326..1327] .))) ;sentence 10 Span:1328..1439 ;To explore this possibility, we compared the methylation status of XRE in ;R9ab cells with that in RK13 cells. ;[1396..1399]:substance:"XRE" (SENT (S (S-PRP (NP-SBJ (-NONE-:[1328..1328] *)) (VP (TO:[1328..1330] To) (VP (VB:[1331..1338] explore) (NP (DT:[1339..1343] this) (NN:[1345..1356] possibility))))) (,:[1356..1357] ,) (NP-SBJ (PRP:[1358..1360] we)) (VP (VBD:[1361..1369] compared) (NP (NP (DT:[1370..1373] the) (NN:[1374..1385] methylation) (NN:[1386..1392] status)) (PP (IN:[1393..1395] of) (NP (NN:[1396..1399] XRE))) (PP-LOC (IN:[1400..1402] in) (NP (NN:[1403..1407] R9ab) (NNS:[1408..1413] cells)))) (PP-CLR (IN:[1414..1418] with) (NP (NP (DT:[1419..1423] that)) (PP-LOC (IN:[1425..1427] in) (NP (NN:[1428..1432] RK13) (NNS:[1433..1438] cells)))))) (.:[1438..1439] .))) ;sentence 11 Span:1440..1603 ;A bisulfite sequence analysis using genomic DNAs from R9ab cells showed that ;the CpG site within XRE was highly methylated on both coding and non-coding ;strands. ;[1442..1451]:substance:"bisulfite" ;[1484..1488]:substance:"DNAs" ;[1522..1525]:substance:"CpG" ;[1538..1541]:substance:"XRE" (SENT (S (NP-SBJ (NP (DT:[1440..1441] A) (NN:[1442..1451] bisulfite) (NN:[1452..1460] sequence) (NN:[1461..1469] analysis)) (VP (VBG:[1470..1475] using) (NP (NP (JJ:[1476..1483] genomic) (NNS:[1484..1488] DNAs)) (PP (IN:[1489..1493] from) (NP (NN:[1494..1498] R9ab) (NNS:[1499..1504] cells)))))) (VP (VBD:[1506..1512] showed) (SBAR (IN:[1513..1517] that) (S (NP-SBJ (NP (DT:[1518..1521] the) (NN:[1522..1525] CpG) (NN:[1526..1530] site)) (PP (IN:[1531..1537] within) (NP (NN:[1538..1541] XRE)))) (VP (VBD:[1542..1545] was) (ADJP-PRD (RB:[1546..1552] highly) (VBN:[1553..1563] methylated)) (PP (IN:[1564..1566] on) (NP (CC:[1567..1571] both) (NML (NML (VBG:[1572..1578] coding) (NML-1 (-NONE-:[1578..1578] *P*))) (CC:[1579..1582] and) (NML (ADJP (AFX:[1584..1587] non) (HYPH:[1587..1588] -) (VBG:[1588..1594] coding)) (NML-1 (NNS:[1595..1602] strands)))))))))) (.:[1602..1603] .))) ;sentence 12 Span:1604..1683 ;In contrast to this result, the hypomethylation of XRE was seen in RK13 ;cells. ;[1655..1658]:substance:"XRE" (SENT (S (PP (IN:[1604..1606] In) (NP (NP (NN:[1607..1615] contrast)) (PP (TO:[1616..1618] to) (NP (DT:[1619..1623] this) (NN:[1624..1630] result))))) (,:[1630..1631] ,) (NP-SBJ-1 (NP (DT:[1632..1635] the) (NN:[1636..1651] hypomethylation)) (PP (IN:[1652..1654] of) (NP (NN:[1655..1658] XRE)))) (VP (VBD:[1659..1662] was) (VP (VBN:[1664..1668] seen) (NP-1 (-NONE-:[1668..1668] *)) (PP-LOC (IN:[1669..1671] in) (NP (NN:[1672..1676] RK13) (NNS:[1677..1682] cells))))) (.:[1682..1683] .))) ;sentence 13 Span:1684..1873 ;To examine whether or not the binding of the AhR/Arnt heterodimer to XRE is ;affected by the methylation status of XRE, a gel shift assay using a ;methylated XRE as a probe was carried out. ;[1729..1732]:substance:"AhR" ;[1733..1737]:substance:"Arnt" ;[1739..1750]:substance:"heterodimer" ;[1754..1757]:substance:"XRE" ;[1799..1802]:substance:"XRE" ;[1842..1845]:substance:"XRE" (SENT (S (S-PRP (NP-SBJ (-NONE-:[1684..1684] *)) (VP (TO:[1684..1686] To) (VP (VB:[1687..1694] examine) (SBAR (IN:[1695..1702] whether) (CC:[1703..1705] or) (RB:[1706..1709] not) (S (NP-SBJ-3 (NP (DT:[1710..1713] the) (NN:[1714..1721] binding)) (PP (IN:[1722..1724] of) (NP (DT:[1725..1728] the) (NML (NN:[1729..1732] AhR) (SYM:[1732..1733] /) (NN:[1733..1737] Arnt)) (NN:[1739..1750] heterodimer))) (PP (TO:[1751..1753] to) (NP (NN:[1754..1757] XRE)))) (VP (VBZ:[1758..1760] is) (VP (VBN:[1761..1769] affected) (NP-3 (-NONE-:[1769..1769] *)) (PP (IN:[1770..1772] by) (NP-LGS (NP (DT:[1773..1776] the) (NN:[1777..1788] methylation) (NN:[1789..1795] status)) (PP (IN:[1796..1798] of) (NP (NN:[1799..1802] XRE)))))))))))) (,:[1802..1803] ,) (NP-SBJ-1 (NP (DT:[1804..1805] a) (NN:[1806..1809] gel) (NN:[1810..1815] shift) (NN:[1817..1822] assay)) (VP (VBG:[1823..1828] using) (NP (DT:[1829..1830] a) (VBN:[1831..1841] methylated) (NN:[1842..1845] XRE)) (PP-MNR (IN:[1846..1848] as) (NP (DT:[1849..1850] a) (NN:[1851..1856] probe))))) (VP (VBD:[1857..1860] was) (VP (VBN:[1861..1868] carried) (PRT (RP:[1869..1872] out)) (NP-1 (-NONE-:[1872..1872] *)))) (.:[1872..1873] .))) ;sentence 14 Span:1874..1946 ;As expected, the AhR/Arnt complex could not bind to the methylated XRE. ;[1892..1895]:substance:"AhR" ;[1896..1900]:substance:"Arnt" ;[1942..1945]:substance:"XRE" (SENT (S (PP (IN:[1874..1876] As) (S-NOM (NP-SBJ-2 (-NONE-:[1876..1876] *)) (VP (VBN:[1877..1885] expected) (NP-2 (-NONE-:[1885..1885] *))))) (,:[1885..1886] ,) (NP-SBJ (DT:[1887..1890] the) (NML (NN:[1892..1895] AhR) (SYM:[1895..1896] /) (NN:[1896..1900] Arnt)) (NN:[1901..1908] complex)) (VP (MD:[1909..1914] could) (RB:[1915..1918] not) (VP (VB:[1919..1923] bind) (PP-CLR (TO:[1924..1926] to) (NP (DT:[1927..1930] the) (VBN:[1931..1941] methylated) (NN:[1942..1945] XRE))))) (.:[1945..1946] .))) ;sentence 15 Span:1947..2078 ;From these results, we conclude that the cell type-specific transcription of ;the rabbit CYP1A1 gene is caused by DNA methylation. ;[2062..2065]:substance:"DNA" (SENT (S (PP (IN:[1947..1951] From) (NP (DT:[1952..1957] these) (NNS:[1958..1965] results))) (,:[1965..1966] ,) (NP-SBJ (PRP:[1967..1969] we)) (VP (VBP:[1971..1979] conclude) (SBAR (IN:[1980..1984] that) (S (NP-SBJ-1 (NP (DT:[1985..1988] the) (ADJP (NML (NN:[1989..1993] cell) (NN:[1994..1998] type)) (HYPH:[1998..1999] -) (JJ:[1999..2007] specific)) (NN:[2008..2021] transcription)) (PP (IN:[2022..2024] of) (NP (DT:[2025..2028] the) (NN:[2029..2035] rabbit) (NN:[2036..2042] CYP1A1) (NN:[2043..2047] gene)))) (VP (VBZ:[2048..2050] is) (VP (VBN:[2052..2058] caused) (NP-1 (-NONE-:[2058..2058] *)) (PP (IN:[2059..2061] by) (NP-LGS (NN:[2062..2065] DNA) (NN:[2066..2077] methylation)))))))) (.:[2077..2078] .))) ;section 16 Span:2079..2109 ;Copyright 1998 Academic Press. (SEC (FRAG (NN:[2079..2088] Copyright) (CD:[2089..2093] 1998) (NNP:[2094..2102] Academic) (NNP:[2103..2108] Press) (.:[2108..2109] .))) ;section 17 Span:2113..2157 ;PMID: 9642136 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2113..2117] PMID) (::[2117..2118] :) (CD:[2119..2126] 9642136) (NN:[2127..2128] -LSB-) (NNP:[2128..2134] PubMed) (::[2135..2136] -) (NN:[2137..2144] indexed) (IN:[2145..2148] for) (NNP:[2149..2157] MEDLINE-RSB-)))