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PubMed:10364157 JSONTXT

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PMID_GLOBAL

Id Subject Object Predicate Lexical cue mondo_id
T1 387-390 DiseaseOrPhenotypicFeature denotes can 0012833
T2 598-613 DiseaseOrPhenotypicFeature denotes erythroleukemia 0017858
T3 688-691 DiseaseOrPhenotypicFeature denotes can 0012833

jnlpba-st-training

Id Subject Object Predicate Lexical cue
T1 22-73 protein denotes hematopoietic transcription factors PU.1 and GATA-1
T2 100-115 cell_type denotes erythroid cells
T3 245-249 protein denotes PU.1
T4 255-309 protein denotes hematopoietic-specific Ets family transcription factor
T5 351-380 cell_type denotes lymphoid and myeloid lineages
T6 382-386 protein denotes PU.1
T7 406-417 protein denotes oncoprotein
T8 592-625 cell_line denotes mouse erythroleukemia (MEL) cells
T9 661-665 protein denotes PU.1
T10 683-687 protein denotes PU.1
T11 768-772 protein denotes PU.1
T12 829-833 protein denotes PU.1
T13 858-864 protein denotes GATA-1
T14 868-900 protein denotes zinc finger transcription factor
T15 961-965 protein denotes PU.1
T16 970-976 protein denotes GATA-1
T17 993-1012 protein denotes DNA-binding domains
T18 1031-1035 protein denotes PU.1
T19 1046-1052 protein denotes GATA-1
T20 1099-1110 protein denotes DNA binding
T21 1115-1138 protein denotes transactivation domains
T22 1142-1146 protein denotes PU.1
T23 1245-1254 cell_line denotes MEL cells
T24 1296-1300 protein denotes PU.1
T25 1424-1430 protein denotes GATA-1
T26 1439-1448 cell_line denotes MEL cells
T27 1541-1545 protein denotes PU.1
T28 1628-1649 protein denotes transcription factors

semrep-sample

Id Subject Object Predicate Lexical cue
E1-ti-1 7-18 cui:C0687133 denotes interaction
E2-ti-1 22-35 cui:C0018957 denotes hematopoietic
E3-ti-1 36-62 cui:C0246120 denotes transcription factors PU.1
E4-ti-1 67-73 cui:C1530719 denotes GATA-1
E5-ti-1 75-85 cui:C0205245 denotes functional
E6-ti-1 86-96 cui:C0680242 denotes antagonism
E7-ti-1 100-115 cui:C1257751 denotes erythroid cells
T1 97-99 LOCATION_OF denotes in
E1-ab-1 117-141 cui:C1608408 denotes Malignant transformation
E2-ab-1 159-167 cui:C0205088 denotes terminal
E3-ab-1 168-172 cui:C0007634 denotes cell
E4-ab-1 205-215 cui:C0441712 denotes mechanisms
E5-ab-1 229-232 cui:C1518422 denotes not
E1-ab-2 255-268 cui:C0018957 denotes hematopoietic
E2-ab-2 282-288 cui:C0015576 denotes family
E3-ab-2 278-309 cui:C0072461 denotes Ets family transcription factor
E4-ab-2 331-342 cui:C1527148 denotes development
E5-ab-2 351-359 cui:C1518071 denotes lymphoid
E6-ab-2 364-371 cui:C0439677 denotes myeloid
E1-ab-3 406-417 cui:C0029005 denotes oncoprotein
E2-ab-3 439-449 cui:C0185117 denotes expression
E3-ab-3 453-462 cui:C1516960 denotes erythroid
E4-ab-3 486-495 cui:C0021107 denotes insertion
E5-ab-3 499-511 cui:C0886519 denotes transgenesis
E6-ab-3 519-535 cui:C0023440 denotes erythroleukemias
E7-ab-3 539-543 cui:C0026809 denotes mice
T2 474-476 METHOD_OF denotes by
T3 512-518 CAUSES denotes causes
T4 536-538 PROCESS_OF denotes in
E1-ab-4 560-568 cui:C0205088 denotes terminal
E2-ab-4 592-597 cui:C0025914 denotes mouse
E3-ab-4 598-613 cui:C0023440 denotes erythroleukemia
E4-ab-4 620-625 cui:C0007634 denotes cells
E5-ab-4 698-707 cui:C1516960 denotes erythroid
E1-ab-5 749-758 cui:C0441712 denotes mechanism
E2-ab-5 789-798 cui:C1516960 denotes erythroid
E1-ab-6 858-864 cui:C1530719 denotes GATA-1
E2-ab-6 868-879 cui:C0080347 denotes zinc finger
E3-ab-6 880-900 cui:C0040648 denotes transcription factor
E4-ab-6 914-923 cui:C1516960 denotes erythroid
E1-ab-7 941-952 cui:C0687133 denotes Interaction
E2-ab-7 970-976 cui:C1530719 denotes GATA-1
E3-ab-7 986-992 cui:C0205266 denotes intact
E4-ab-7 993-1012 cui:C1511662 denotes DNA-binding domains
E5-ab-7 1021-1029 cui:C0033684 denotes proteins
T5 1013-1015 COEXISTS_WITH denotes in
E1-ab-8 1046-1052 cui:C1530719 denotes GATA-1
E2-ab-8 1053-1061 cui:C0086597 denotes mediated
E3-ab-8 1062-1088 cui:C0162493 denotes transcriptional activation
E1-ab-9 1099-1110 cui:C1148673 denotes DNA binding
E2-ab-9 1115-1130 cui:C0040624 denotes transactivation
E3-ab-9 1164-1174 cui:C0035143 denotes repression
E4-ab-9 1217-1225 cui:C0205088 denotes terminal
E5-ab-9 1245-1248 cui:C0025914 denotes MEL
E6-ab-9 1245-1248 cui:C0023440 denotes MEL
E7-ab-9 1249-1254 cui:C0007634 denotes cells
E1-ab-10 1274-1292 cui:C1512167 denotes ectopic expression
E2-ab-10 1304-1311 cui:C0043342 denotes Xenopus
E3-ab-10 1312-1319 cui:C0013935 denotes embryos
E4-ab-10 1323-1333 cui:C0205410 denotes sufficient
E5-ab-10 1343-1357 cui:C0014819 denotes erythropoiesis
E6-ab-10 1365-1371 cui:C0205307 denotes normal
E7-ab-10 1372-1383 cui:C1527148 denotes development
T6 1304-1319 PART_OF denotes Xenopus embryos
T7 1337-1342 AFFECTS denotes block
E1-ab-11 1398-1410 cui:C1293116 denotes introduction
E2-ab-11 1414-1423 cui:C0205228 denotes exogenous
E3-ab-11 1424-1430 cui:C1530719 denotes GATA-1
E4-ab-11 1439-1442 cui:C0025914 denotes MEL
E5-ab-11 1439-1442 cui:C0023440 denotes MEL
E6-ab-11 1443-1448 cui:C0007634 denotes cells
E7-ab-11 1453-1460 cui:C0043342 denotes Xenopus
E8-ab-11 1461-1468 cui:C0013935 denotes embryos
E9-ab-11 1495-1500 cui:C0028778 denotes block
E10-ab-11 1504-1513 cui:C1516960 denotes erythroid
T8 1431-1433 LOCATION_OF denotes in
T9 1431-1433 LOCATION_OF denotes in
T10 1453-1468 PART_OF denotes Xenopus embryos
T11 1482-1490 TREATS denotes relieves
E1-ab-12 1551-1558 cui:C1274040 denotes results
E2-ab-12 1577-1590 cui:C0597526 denotes stoichiometry
E3-ab-12 1628-1649 cui:C0040648 denotes transcription factors
E4-ab-12 1689-1698 cui:C1522240 denotes processes
E5-ab-12 1702-1708 cui:C0205307 denotes normal
E6-ab-12 1729-1753 cui:C1608408 denotes malignant transformation
R1 E7-ti-1 T1 subjectOf erythroid cells,in
R2 E4-ti-1 T1 objectOf GATA-1,in
R3 E4-ab-3 T2 subjectOf insertion,by
R4 E2-ab-3 T2 objectOf expression,by
R5 E1-ab-3 T3 subjectOf oncoprotein,causes
R6 E6-ab-3 T3 objectOf erythroleukemias,causes
R7 E6-ab-3 T4 subjectOf erythroleukemias,in
R8 E7-ab-3 T4 objectOf mice,in
R9 E2-ab-7 T5 subjectOf GATA-1,in
R10 E5-ab-7 T5 objectOf proteins,in
R11 E3-ab-10 T6 subjectOf embryos,Xenopus embryos
R12 E2-ab-10 T6 objectOf Xenopus,Xenopus embryos
R13 E1-ab-10 T7 subjectOf ectopic expression,block
R14 E5-ab-10 T7 objectOf erythropoiesis,block
R15 E6-ab-11 T8 subjectOf cells,in
R16 E3-ab-11 T8 objectOf GATA-1,in
R17 E8-ab-11 T9 subjectOf embryos,in
R18 E3-ab-11 T9 objectOf GATA-1,in
R19 E8-ab-11 T10 subjectOf embryos,Xenopus embryos
R20 E7-ab-11 T10 objectOf Xenopus,Xenopus embryos
R21 E1-ab-11 T11 subjectOf introduction,relieves
R22 E9-ab-11 T11 objectOf block,relieves

pubmed-sentences-benchmark

Id Subject Object Predicate Lexical cue
S1 0-116 Sentence denotes Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells.
S2 117-244 Sentence denotes Malignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood.
S3 245-381 Sentence denotes PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages.
S4 382-544 Sentence denotes PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice.
S5 545-724 Sentence denotes Restoration of terminal differentiation in the mouse erythroleukemia (MEL) cells requires a decline in the level of PU.1, indicating that PU.1 can block erythroid differentiation.
S6 725-815 Sentence denotes Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation.
S7 816-940 Sentence denotes We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation.
S8 941-1030 Sentence denotes Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins.
S9 1031-1089 Sentence denotes PU.1 represses GATA-1-mediated transcriptional activation.
S10 1090-1255 Sentence denotes Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells.
S11 1256-1384 Sentence denotes We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development.
S12 1385-1546 Sentence denotes Furthermore, introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1.
S13 1547-1754 Sentence denotes Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation.

genia-medco-coref

Id Subject Object Predicate Lexical cue
C1 22-73 NP denotes hematopoietic transcription factors PU.1 and GATA-1
C2 117-141 NP denotes Malignant transformation
C3 245-249 NP denotes PU.1
C4 253-309 NP denotes a hematopoietic-specific Ets family transcription factor
C5 310-314 NP denotes that
C6 382-386 NP denotes PU.1
C7 435-438 NP denotes its
C8 560-625 NP denotes terminal differentiation in the mouse erythroleukemia (MEL) cells
C9 661-665 NP denotes PU.1
C10 683-687 NP denotes PU.1
C11 698-723 NP denotes erythroid differentiation
C12 745-758 NP denotes the mechanism
C13 762-767 NP denotes which
C14 768-772 NP denotes PU.1
C15 789-814 NP denotes erythroid differentiation
C16 829-833 NP denotes PU.1
C17 858-864 NP denotes GATA-1
C19 914-939 NP denotes erythroid differentiation
C18 866-939 NP denotes a zinc finger transcription factor required for erythroid differentiation
C21 961-965 NP denotes PU.1
C22 970-976 NP denotes GATA-1
C20 961-976 NP denotes PU.1 and GATA-1
C23 1016-1029 NP denotes both proteins
C24 1031-1035 NP denotes PU.1
C26 1142-1146 NP denotes PU.1
C25 1090-1146 NP denotes Both the DNA binding and transactivation domains of PU.1
C27 1179-1191 NP denotes both domains
C28 1217-1254 NP denotes terminal differentiation in MEL cells
C29 1296-1300 NP denotes PU.1
C30 1541-1545 NP denotes PU.1
C31 1729-1753 NP denotes malignant transformation
R1 C5 C4 coref-relat that,a hematopoietic-specific Ets family transcription factor
R2 C6 C3 coref-ident PU.1,PU.1
R3 C7 C6 coref-pron its,PU.1
R4 C9 C6 coref-ident PU.1,PU.1
R5 C10 C9 coref-ident PU.1,PU.1
R6 C13 C12 coref-relat which,the mechanism
R7 C14 C10 coref-ident PU.1,PU.1
R8 C15 C11 coref-ident erythroid differentiation,erythroid differentiation
R9 C16 C14 coref-ident PU.1,PU.1
R10 C19 C15 coref-ident erythroid differentiation,erythroid differentiation
R11 C18 C17 coref-appos a zinc finger transcription factor required for erythroid differentiation,GATA-1
R12 C21 C16 coref-ident PU.1,PU.1
R13 C22 C17 coref-ident GATA-1,GATA-1
R14 C20 C1 coref-ident PU.1 and GATA-1,hematopoietic transcription factors PU.1 and GATA-1
R15 C23 C20 coref-ident both proteins,PU.1 and GATA-1
R16 C24 C21 coref-ident PU.1,PU.1
R17 C26 C24 coref-ident PU.1,PU.1
R18 C27 C25 coref-ident both domains,Both the DNA binding and transactivation domains of PU.1
R19 C28 C8 coref-ident terminal differentiation in MEL cells,terminal differentiation in the mouse erythroleukemia (MEL) cells
R20 C29 C26 coref-ident PU.1,PU.1
R21 C30 C29 coref-ident PU.1,PU.1
R22 C31 C2 coref-ident malignant transformation,Malignant transformation

GENIAcorpus

Id Subject Object Predicate Lexical cue
T1 100-115 cell_type denotes erythroid cells
T2 117-141 other_name denotes Malignant transformation
T3 159-188 other_name denotes terminal cell differentiation
T4 245-249 protein_molecule denotes PU.1
T5 255-309 protein_molecule denotes hematopoietic-specific Ets family transcription factor
T6 382-386 protein_molecule denotes PU.1
T7 406-417 protein_family_or_group denotes oncoprotein
T8 453-473 other_name denotes erythroid precursors
T9 477-495 other_name denotes proviral insertion
T10 499-511 other_name denotes transgenesis
T11 519-535 other_name denotes erythroleukemias
T12 539-543 multi_cell denotes mice
T13 560-584 other_name denotes terminal differentiation
T14 592-615 cell_line denotes mouse erythroleukemia (
T15 615-618 cell_line denotes MEL
T16 661-665 protein_molecule denotes PU.1
T17 683-687 protein_molecule denotes PU.1
T18 698-723 other_name denotes erythroid differentiation
T19 768-772 protein_molecule denotes PU.1
T20 789-814 other_name denotes erythroid differentiation
T21 829-833 protein_molecule denotes PU.1
T22 858-864 protein_molecule denotes GATA-1
T23 868-900 protein_family_or_group denotes zinc finger transcription factor
T24 914-939 other_name denotes erythroid differentiation
T25 961-965 protein_molecule denotes PU.1
T26 970-976 protein_molecule denotes GATA-1
T27 993-1012 protein_domain_or_region denotes DNA-binding domains
T28 1031-1035 protein_molecule denotes PU.1
T29 1046-1052 protein_molecule denotes GATA-1
T30 1099-1110 protein_domain_or_region denotes DNA binding
T31 1115-1138 protein_domain_or_region denotes transactivation domains
T32 1142-1146 protein_molecule denotes PU.1
T33 1217-1241 other_name denotes terminal differentiation
T34 1245-1254 cell_line denotes MEL cells
T35 1274-1292 other_name denotes ectopic expression
T36 1296-1300 protein_molecule denotes PU.1
T37 1304-1319 multi_cell denotes Xenopus embryos
T38 1343-1357 other_name denotes erythropoiesis
T39 1424-1430 protein_molecule denotes GATA-1
T40 1439-1448 cell_line denotes MEL cells
T41 1453-1468 multi_cell denotes Xenopus embryos
T42 1504-1529 other_name denotes erythroid differentiation
T43 1541-1545 protein_molecule denotes PU.1
T44 1628-1649 protein_family_or_group denotes transcription factors

metamap-sample

Id Subject Object Predicate Lexical cue
T1 1425-1431 C1530719 denotes ATA-1
T2 1047-1053 C1530719 denotes ATA-1-
T3 971-977 C1530719 denotes ATA-1
T4 859-865 C1530719 denotes ATA-1,
T5 68-74 C1530719 denotes ATA-1:
T6 101-116 C1257751 denotes rythroid cells.
T7 1440-1443 C0026809 denotes EL
T8 1246-1249 C0026809 denotes EL
T9 593-597 C0026809 denotes ouse
T10 540-544 C0026809 denotes ice.
T11 87-97 C0680242 denotes ntagonism
T12 942-953 C1704675 denotes nteraction
T13 8-19 C1704675 denotes nteraction
T14 23-63 C0919490 denotes ematopoietic transcription factors PU.1
T15 76-86 C2700217 denotes unctional
T16 1-7 C0439851 denotes irect
T17 1440-1443 C0023440 denotes EL
T18 1246-1249 C0023440 denotes EL
T19 599-614 C0023440 denotes rythroleukemia
T20 520-536 C0023440 denotes rythroleukemias
T21 1710-1725 C0007589 denotes ifferentiation
T22 1515-1529 C0007589 denotes ifferentiation
T23 925-940 C0007589 denotes ifferentiation.
T24 800-815 C0007589 denotes ifferentiation.
T25 709-724 C0007589 denotes ifferentiation.
T26 169-189 C0007589 denotes ell differentiation
T27 1454-1461 C0043343 denotes enopus
T28 1305-1312 C0043343 denotes enopus
T29 1542-1546 C1705644 denotes U.1.
T30 1297-1301 C1705644 denotes U.1
T31 1143-1147 C1705644 denotes U.1
T32 1032-1036 C1705644 denotes U.1
T33 962-966 C1705644 denotes U.1
T34 830-833 C1705644 denotes U.1
T35 769-773 C1705644 denotes U.1
T36 684-688 C1705644 denotes U.1
T37 383-387 C1705644 denotes U.1
T38 246-250 C1705644 denotes U.1
T39 1629-1650 C0040648 denotes ranscription factors
T40 881-901 C0040648 denotes ranscription factor
T41 290-310 C0040648 denotes ranscription factor
T42 397-400 C0079613 denotes ct
T43 869-880 C0080347 denotes inc finger
T44 1505-1514 C1516960 denotes rythroid
T45 915-924 C1516960 denotes rythroid
T46 790-799 C1516960 denotes rythroid
T47 699-708 C1516960 denotes rythroid
T48 454-463 C1516960 denotes rythroid
T49 487-496 C1512796 denotes nsertion
T50 1344-1358 C0014819 denotes rythropoiesis
T51 1496-1501 C2828370 denotes lock
T52 1338-1343 C2828370 denotes lock
T53 1212-1216 C2828370 denotes lock
T54 693-698 C2828370 denotes lock
T55 513-518 C1314792 denotes auses
T56 1202-1208 C0027552 denotes eeded
T57 234-244 C0162340 denotes nderstood.
T58 1063-1089 C0162493 denotes ranscriptional activation.
T59 290-303 C0040649 denotes ranscription
T60 407-418 C0029005 denotes ncoprotein
T61 1116-1131 C0040624 denotes ransactivation
T62 500-512 C0886519 denotes ransgenesis
T63 1006-1013 C1883221 denotes omains
T64 1218-1242 C2752630 denotes erminal differentiation
T65 561-585 C2752630 denotes erminal differentiation
T66 1152-1160 C1514873 denotes equired
T67 902-910 C1514873 denotes equired
T68 319-327 C1514873 denotes equired
T69 1444-1449 C0007634 denotes ells
T70 1250-1255 C0007634 denotes ells.
T71 621-626 C0007634 denotes ells
T72 151-159 C0018790 denotes nhibits
T73 1165-1175 C0035143 denotes epression
T74 283-289 C0015576 denotes amily
T75 1462-1469 C0013935 denotes mbryos
T76 1313-1320 C0013935 denotes mbryos
T77 1740-1754 C0040682 denotes ransformation.
T78 128-142 C0040682 denotes ransformation
T79 750-759 C0441712 denotes echanism
T80 206-216 C0441712 denotes echanisms
T81 1595-1602 C1947931 denotes irectly
T82 845-853 C1947931 denotes irectly
T83 1373-1384 C0678723 denotes evelopment.
T84 332-343 C0678723 denotes evelopment
T85 1730-1739 C0205282 denotes alignant
T86 118-127 C0205282 denotes alignant
T87 1218-1226 C0205088 denotes erminal
T88 160-168 C0205088 denotes erminal
T89 422-432 C1879547 denotes ctivation
T90 1100-1111 C1148673 denotes NA binding
T91 440-450 C0185117 denotes xpression
T92 820-824 C0243095 denotes ind
T93 734-745 C1292732 denotes nvestigate
T94 217-225 C1314939 denotes nvolved
T95 230-233 C1518422 denotes ot
T96 1483-1491 C1301676 denotes elieves
T97 1265-1269 C1547282 denotes how
T98 1209-1211 C1883351 denotes o
T99 1552-1559 C2825142 denotes esults
T100 1324-1334 C0205410 denotes ufficient
T101 774-789 C0521102 denotes nterferes with
T102 373-381 C1881379 denotes ineages.
T103 464-474 C1709634 denotes recursors
T104 1275-1293 C1512167 denotes ctopic expression
T105 546-557 C0449982 denotes estoration
T106 1399-1411 C1293116 denotes ntroduction
T107 1578-1591 C0597526 denotes toichiometry
T108 352-359 C1518071 denotes ymphoid
T109 1690-1699 C1522240 denotes rocesses
T110 365-372 C0439677 denotes yeloid
T111 198-205 C2939802 denotes recise
T112 169-173 C1269647 denotes ell
T113 1054-1061 C0086597 denotes ediated
T114 256-269 C0229601 denotes ematopoietic-
T115 270-278 C0205369 denotes pecific
T116 1415-1424 C0205101 denotes xogenous
T117 987-992 C0205266 denotes ntact
T118 1668-1678 C1521761 denotes eterminant
T119 1703-1709 C0439166 denotes ormal

2015-BEL-Sample-2

Id Subject Object Predicate Lexical cue
BEL:20045098 117-1753 p(HGNC:SP1) increases r(HGNC:GATA1) denotes Malignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood. PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages. PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice. Restoration of terminal differentiation in the mouse erythroleukemia (MEL) cells requires a decline in the level of PU.1, indicating that PU.1 can block erythroid differentiation. Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation. We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation. Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells. We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development. Furthermore, introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1. Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation
BEL:20068226 0-1753 tscript(p(MGI:Gata1)) directlyIncreases r(MGI:Nfe2) denotes Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Malignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood. PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages. PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice. Restoration of terminal differentiation in the mouse erythroleukemia (MEL) cells requires a decline in the level of PU.1, indicating that PU.1 can block erythroid differentiation. Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation. We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation. Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells. We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development. Furthermore, introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1. Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation
BEL:20068226 0-1753 tscript(p(MGI:Gata1)) directlyIncreases r(MGI:Nfe2) denotes Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Malignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood. PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages. PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice. Restoration of terminal differentiation in the mouse erythroleukemia (MEL) cells requires a decline in the level of PU.1, indicating that PU.1 can block erythroid differentiation. Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation. We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation. Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells. We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development. Furthermore, introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1. Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation
BEL:20065868 0-1753 tscript(p(HGNC:GATA1)) directlyIncreases r(HGNC:NFE2) denotes Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Malignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood. PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages. PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice. Restoration of terminal differentiation in the mouse erythroleukemia (MEL) cells requires a decline in the level of PU.1, indicating that PU.1 can block erythroid differentiation. Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation. We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation. Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells. We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development. Furthermore, introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1. Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation