J. Comput. Biol. - Chromatin properties of regulatory DNA probed by manipulation of transcription factors.

Tópicos

{ bind(1733) structur(1185) ligand(1036) }
{ gene(2352) biolog(1181) express(1162) }
{ cost(1906) reduc(1198) effect(832) }
{ result(1111) use(1088) new(759) }
{ activ(1452) weight(1219) physic(1104) }
{ can(774) often(719) complex(702) }
{ assess(1506) score(1403) qualiti(1306) }
{ model(2341) predict(2261) use(1141) }
{ use(1733) differ(960) four(931) }
{ problem(2511) optim(1539) algorithm(950) }
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{ compound(1573) activ(1297) structur(1058) }
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{ sampl(1606) size(1419) use(1276) }
{ use(976) code(926) identifi(902) }
{ drug(1928) target(777) effect(648) }
{ model(3404) distribut(989) bayesian(671) }
{ imag(1947) propos(1133) code(1026) }
{ data(1737) use(1416) pattern(1282) }
{ inform(2794) health(2639) internet(1427) }
{ system(1976) rule(880) can(841) }
{ measur(2081) correl(1212) valu(896) }
{ imag(1057) registr(996) error(939) }
{ sequenc(1873) structur(1644) protein(1328) }
{ method(1219) similar(1157) match(930) }
{ featur(3375) classif(2383) classifi(1994) }
{ imag(2830) propos(1344) filter(1198) }
{ network(2748) neural(1063) input(814) }
{ imag(2675) segment(2577) method(1081) }
{ patient(2315) diseas(1263) diabet(1191) }
{ take(945) account(800) differ(722) }
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{ motion(1329) object(1292) video(1091) }
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{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ signal(2180) analysi(812) frequenc(800) }
{ group(2977) signific(1463) compar(1072) }
{ data(3008) multipl(1320) sourc(1022) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
{ activ(1138) subject(705) human(624) }
{ time(1939) patient(1703) rate(768) }
{ patient(1821) servic(1111) care(1106) }
{ use(2086) technolog(871) perceiv(783) }
{ can(981) present(881) function(850) }
{ analysi(2126) use(1163) compon(1037) }
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{ high(1669) rate(1365) level(1280) }
{ cancer(2502) breast(956) screen(824) }
{ implement(1333) system(1263) develop(1122) }
{ survey(1388) particip(1329) question(1065) }
{ estim(2440) model(1874) function(577) }
{ decis(3086) make(1611) patient(1517) }
{ process(1125) use(805) approach(778) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

Transcription factors (TFs) bind to DNA and regulate the transcription of nearby genes. However, only a small fraction of TF binding sites have such regulatory effects. Here we search for the predictors of functional binding sites by carrying out a systematic computational screening of a variety of contextual factors (histone modifications, nuclear lamin-bindings, and cofactor bindings). We used regression analysis to test if contextual factors are associated with upregulation or downregulation of neighboring genes following the induction or knockdown of the 9 TFs in mouse embryonic stem (ES) cells. Functional TF binding sites appeared to be either active (i.e., bound by P300, CHD7, mediator, cohesin, and SWI/SNF) or repressed (i.e., with H3K27me3 histone marks and bound by Polycomb factors). Active binding sites mediated the downregulation of nearby genes upon knocking down the activating TFs or inducing repressors. Repressed TF binding sites mediated the upregulation of nearby genes (e.g., poised developmental regulators) upon inducing TFs. In addition, repressed binding sites mediated repressive effects of TFs, identified by the downregulation of target genes after the induction of TFs or by the upregulation of target genes after the knockdown of TFs. The contextual factors associated with functions of DNA-bound TFs were used to improve the identification of candidate target genes regulated by TFs.

Resumo Limpo

transcript factor tfs bind dna regul transcript nearbi gene howev small fraction tf bind site regulatori effect search predictor function bind site carri systemat comput screen varieti contextu factor histon modif nuclear laminbind cofactor bind use regress analysi test contextu factor associ upregul downregul neighbor gene follow induct knockdown tfs mous embryon stem es cell function tf bind site appear either activ ie bound p chd mediat cohesin swisnf repress ie hkme histon mark bound polycomb factor activ bind site mediat downregul nearbi gene upon knock activ tfs induc repressor repress tf bind site mediat upregul nearbi gene eg pois development regul upon induc tfs addit repress bind site mediat repress effect tfs identifi downregul target gene induct tfs upregul target gene knockdown tfs contextu factor associ function dnabound tfs use improv identif candid target gene regul tfs

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