c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression
The c-myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define its role during the hematopoietic lineage commitment, we silenced c-myb in human CD34(+) hematopoietic stem/progenitor cells. Noteworthy, c-myb silencing increased...
Uloženo v:
| Vydáno v: | Blood Ročník 116; číslo 22; s. e99 |
|---|---|
| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
25.11.2010
|
| Témata: | |
| ISSN: | 1528-0020, 1528-0020 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | The c-myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define its role during the hematopoietic lineage commitment, we silenced c-myb in human CD34(+) hematopoietic stem/progenitor cells. Noteworthy, c-myb silencing increased the commitment capacity toward the macrophage and megakaryocyte lineages, whereas erythroid differentiation was impaired, as demonstrated by clonogenic assay, morphologic and immunophenotypic data. Gene expression profiling and computational analysis of promoter regions of genes modulated in c-myb-silenced CD34(+) cells identified the transcription factors Kruppel-Like Factor 1 (KLF1) and LIM Domain Only 2 (LMO2) as putative targets, which can account for c-myb knockdown effects. Indeed, chromatin immunoprecipitation and luciferase reporter assay demonstrated that c-myb binds to KLF1 and LMO2 promoters and transactivates their expression. Consistently, the retroviral vector-mediated overexpression of either KLF1 or LMO2 partially rescued the defect in erythropoiesis caused by c-myb silencing, whereas only KLF1 was also able to repress the megakaryocyte differentiation enhanced in Myb-silenced CD34(+) cells. Our data collectively demonstrate that c-myb plays a pivotal role in human primary hematopoietic stem/progenitor cells lineage commitment, by enhancing erythropoiesis at the expense of megakaryocyte diffentiation. Indeed, we identified KLF1 and LMO2 transactivation as the molecular mechanism underlying Myb-driven erythroid versus megakaryocyte cell fate decision. |
|---|---|
| AbstractList | The c-myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define its role during the hematopoietic lineage commitment, we silenced c-myb in human CD34(+) hematopoietic stem/progenitor cells. Noteworthy, c-myb silencing increased the commitment capacity toward the macrophage and megakaryocyte lineages, whereas erythroid differentiation was impaired, as demonstrated by clonogenic assay, morphologic and immunophenotypic data. Gene expression profiling and computational analysis of promoter regions of genes modulated in c-myb-silenced CD34(+) cells identified the transcription factors Kruppel-Like Factor 1 (KLF1) and LIM Domain Only 2 (LMO2) as putative targets, which can account for c-myb knockdown effects. Indeed, chromatin immunoprecipitation and luciferase reporter assay demonstrated that c-myb binds to KLF1 and LMO2 promoters and transactivates their expression. Consistently, the retroviral vector-mediated overexpression of either KLF1 or LMO2 partially rescued the defect in erythropoiesis caused by c-myb silencing, whereas only KLF1 was also able to repress the megakaryocyte differentiation enhanced in Myb-silenced CD34(+) cells. Our data collectively demonstrate that c-myb plays a pivotal role in human primary hematopoietic stem/progenitor cells lineage commitment, by enhancing erythropoiesis at the expense of megakaryocyte diffentiation. Indeed, we identified KLF1 and LMO2 transactivation as the molecular mechanism underlying Myb-driven erythroid versus megakaryocyte cell fate decision. The c-myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define its role during the hematopoietic lineage commitment, we silenced c-myb in human CD34(+) hematopoietic stem/progenitor cells. Noteworthy, c-myb silencing increased the commitment capacity toward the macrophage and megakaryocyte lineages, whereas erythroid differentiation was impaired, as demonstrated by clonogenic assay, morphologic and immunophenotypic data. Gene expression profiling and computational analysis of promoter regions of genes modulated in c-myb-silenced CD34(+) cells identified the transcription factors Kruppel-Like Factor 1 (KLF1) and LIM Domain Only 2 (LMO2) as putative targets, which can account for c-myb knockdown effects. Indeed, chromatin immunoprecipitation and luciferase reporter assay demonstrated that c-myb binds to KLF1 and LMO2 promoters and transactivates their expression. Consistently, the retroviral vector-mediated overexpression of either KLF1 or LMO2 partially rescued the defect in erythropoiesis caused by c-myb silencing, whereas only KLF1 was also able to repress the megakaryocyte differentiation enhanced in Myb-silenced CD34(+) cells. Our data collectively demonstrate that c-myb plays a pivotal role in human primary hematopoietic stem/progenitor cells lineage commitment, by enhancing erythropoiesis at the expense of megakaryocyte diffentiation. Indeed, we identified KLF1 and LMO2 transactivation as the molecular mechanism underlying Myb-driven erythroid versus megakaryocyte cell fate decision.The c-myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define its role during the hematopoietic lineage commitment, we silenced c-myb in human CD34(+) hematopoietic stem/progenitor cells. Noteworthy, c-myb silencing increased the commitment capacity toward the macrophage and megakaryocyte lineages, whereas erythroid differentiation was impaired, as demonstrated by clonogenic assay, morphologic and immunophenotypic data. Gene expression profiling and computational analysis of promoter regions of genes modulated in c-myb-silenced CD34(+) cells identified the transcription factors Kruppel-Like Factor 1 (KLF1) and LIM Domain Only 2 (LMO2) as putative targets, which can account for c-myb knockdown effects. Indeed, chromatin immunoprecipitation and luciferase reporter assay demonstrated that c-myb binds to KLF1 and LMO2 promoters and transactivates their expression. Consistently, the retroviral vector-mediated overexpression of either KLF1 or LMO2 partially rescued the defect in erythropoiesis caused by c-myb silencing, whereas only KLF1 was also able to repress the megakaryocyte differentiation enhanced in Myb-silenced CD34(+) cells. Our data collectively demonstrate that c-myb plays a pivotal role in human primary hematopoietic stem/progenitor cells lineage commitment, by enhancing erythropoiesis at the expense of megakaryocyte diffentiation. Indeed, we identified KLF1 and LMO2 transactivation as the molecular mechanism underlying Myb-driven erythroid versus megakaryocyte cell fate decision. |
| Author | Tenedini, Elena Zini, Roberta Bianchi, Elisa Tagliafico, Enrico Manfredini, Rossella Ferrari, Sergio Salati, Simona Norfo, Ruggiero |
| Author_xml | – sequence: 1 givenname: Elisa surname: Bianchi fullname: Bianchi, Elisa organization: Department of Biomedical Sciences, Biological Chemistry Section, University of Modena and Reggio Emilia, Modena, Italy – sequence: 2 givenname: Roberta surname: Zini fullname: Zini, Roberta – sequence: 3 givenname: Simona surname: Salati fullname: Salati, Simona – sequence: 4 givenname: Elena surname: Tenedini fullname: Tenedini, Elena – sequence: 5 givenname: Ruggiero surname: Norfo fullname: Norfo, Ruggiero – sequence: 6 givenname: Enrico surname: Tagliafico fullname: Tagliafico, Enrico – sequence: 7 givenname: Rossella surname: Manfredini fullname: Manfredini, Rossella – sequence: 8 givenname: Sergio surname: Ferrari fullname: Ferrari, Sergio |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20686118$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkLFOwzAYhC1URNvAGyDkjcnw23FcZ0QVBURQFzpHduzQoCQOtoPo2xNEkZjudHe64VuiWe96i9AlhRtKJbvVrXOGMICcgCQslSmlJ2hBMyYJAIPZPz9HyxDeAShPWXaG5gyEFNPLAu0q0h00DuMwOB8Dtv4Q994NrrGhCfjHj2_7SS2OXvVBVbH5VLFxPXY1fi42FKve4OJly7D9GrwNYerO0Wmt2mAvjpqg3eb-df1Iiu3D0_quIBVnq0hMnWZUCmOUERxEVa_yNNMGtEhBKphiznVG85VkUuVVLixTUFtRU9BWac4SdP37O3j3MdoQy64JlW1b1Vs3hlJSzkWWTQgSdHVcjrqzphx80yl_KP9IsG-LUWQd |
| CitedBy_id | crossref_primary_10_1128_MCB_01617_12 crossref_primary_10_1182_blood_2010_11_316893 crossref_primary_10_1016_j_exphem_2015_10_007 crossref_primary_10_1177_15353702211028195 crossref_primary_10_3390_ijms252211886 crossref_primary_10_1182_blood_2015_07_607952 crossref_primary_10_1093_ndt_gfs513 crossref_primary_10_1002_stem_2834 crossref_primary_10_1038_s41590_023_01662_3 crossref_primary_10_1016_j_jprot_2013_10_040 crossref_primary_10_1016_j_bcmd_2017_06_001 crossref_primary_10_1111_j_1600_0609_2012_01774_x crossref_primary_10_1016_j_exphem_2018_03_004 crossref_primary_10_1097_MOH_0b013e32835f59ba crossref_primary_10_1080_03630269_2018_1482832 crossref_primary_10_1002_wrna_1537 crossref_primary_10_1007_s40291_022_00589_z crossref_primary_10_1016_j_bcmd_2017_08_001 crossref_primary_10_1371_journal_pone_0196400 crossref_primary_10_1186_s40169_016_0092_7 crossref_primary_10_3390_ijms22179615 crossref_primary_10_1016_j_exphem_2015_06_008 crossref_primary_10_3389_fcell_2021_640060 crossref_primary_10_1371_journal_pone_0129431 crossref_primary_10_1177_1535370215596859 crossref_primary_10_1172_JCI71520 crossref_primary_10_3390_ijms22189808 crossref_primary_10_1146_annurev_genom_083117_021320 crossref_primary_10_1002_sctm_17_0192 crossref_primary_10_1016_j_celrep_2024_114378 crossref_primary_10_1073_pnas_1018384108 crossref_primary_10_1002_ijc_29920 crossref_primary_10_1016_j_gde_2015_08_001 crossref_primary_10_1182_blood_2013_12_544197 crossref_primary_10_1016_j_exphem_2021_02_004 crossref_primary_10_3390_ijms18010145 crossref_primary_10_1111_jcmm_13917 crossref_primary_10_1182_blood_2014_08_590968 crossref_primary_10_1016_j_blre_2018_06_001 crossref_primary_10_3109_03630269_2011_615876 crossref_primary_10_1002_1878_0261_12387 crossref_primary_10_1186_s12920_015_0120_2 crossref_primary_10_1016_j_hoc_2013_11_009 crossref_primary_10_1016_j_gene_2018_04_065 crossref_primary_10_1097_MOH_0000000000000625 crossref_primary_10_1038_s41467_020_17100_z crossref_primary_10_1371_journal_pone_0133280 crossref_primary_10_1016_j_exphem_2012_08_003 crossref_primary_10_1042_BJ20130628 crossref_primary_10_1371_journal_pone_0091557 crossref_primary_10_1073_pnas_1016166108 crossref_primary_10_1074_jbc_M112_350496 crossref_primary_10_1111_bjh_13909 crossref_primary_10_1016_j_bcmd_2018_01_004 crossref_primary_10_1128_MCB_01058_12 crossref_primary_10_3390_genes14030577 crossref_primary_10_1097_MOH_0000000000000333 crossref_primary_10_1371_journal_pone_0053496 crossref_primary_10_1186_1471_2164_13_153 crossref_primary_10_1007_s11515_015_1365_z crossref_primary_10_1038_cdd_2015_30 crossref_primary_10_1084_jem_20201729 crossref_primary_10_3390_v15030713 crossref_primary_10_1016_j_jcyt_2018_04_003 crossref_primary_10_1089_scd_2016_0150 crossref_primary_10_3233_CH_189004 crossref_primary_10_1016_j_exphem_2012_04_007 crossref_primary_10_1038_s41598_025_94222_8 crossref_primary_10_1182_blood_2011_03_331371 crossref_primary_10_1096_fj_13_242669 crossref_primary_10_1182_blood_2016_01_693705 crossref_primary_10_1186_1476_4598_10_21 crossref_primary_10_1038_s41467_024_49289_8 crossref_primary_10_1038_s41598_021_89641_2 crossref_primary_10_1371_journal_pone_0075815 crossref_primary_10_1089_scd_2017_0137 crossref_primary_10_1128_MCB_00714_14 crossref_primary_10_1007_s00439_016_1688_0 crossref_primary_10_1182_blood_2012_06_292078 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1182/blood-2009-08-238311 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine Chemistry Biology Anatomy & Physiology |
| EISSN | 1528-0020 |
| ExternalDocumentID | 20686118 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | --- -~X .55 0R~ 23N 2WC 34G 39C 4.4 53G 5GY 5RE 5VS 6J9 9M8 AAEDW AAXUO ABOCM ACGFO ADBBV ADVLN AENEX AFFNX AFOSN AITUG AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ BAWUL BTFSW CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF EJD EX3 F5P FDB FRP GS5 GX1 H13 IH2 K-O KQ8 L7B LSO MJL N4W N9A NPM OK1 P2P R.V RHI ROL SJN THE TR2 TWZ W2D W8F WH7 WOQ WOW X7M YHG YKV 7X8 AALRI ACVFH ADCNI AEUPX AFPUW AIGII AKBMS AKYEP EFKBS |
| ID | FETCH-LOGICAL-c427t-df35186ddad6406cf7935bd0b6308a0dad44b5197828a9c96e2a0fe6f10beab42 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 89 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000284599900001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1528-0020 |
| IngestDate | Sun Sep 28 10:04:53 EDT 2025 Thu Apr 03 06:53:39 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 22 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c427t-df35186ddad6406cf7935bd0b6308a0dad44b5197828a9c96e2a0fe6f10beab42 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://dx.doi.org/10.1182/blood-2009-08-238311 |
| PMID | 20686118 |
| PQID | 814465500 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_814465500 pubmed_primary_20686118 |
| PublicationCentury | 2000 |
| PublicationDate | 2010-Nov-25 20101125 |
| PublicationDateYYYYMMDD | 2010-11-25 |
| PublicationDate_xml | – month: 11 year: 2010 text: 2010-Nov-25 day: 25 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Blood |
| PublicationTitleAlternate | Blood |
| PublicationYear | 2010 |
| SSID | ssj0014325 |
| Score | 2.327823 |
| Snippet | The c-myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define its role during the... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | e99 |
| SubjectTerms | Adaptor Proteins, Signal Transducing Antigens, CD34 - metabolism Cells, Cultured DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Erythropoiesis Gene Expression Regulation Gene Silencing Granulocyte Precursor Cells - cytology Granulocyte Precursor Cells - metabolism Humans Kruppel-Like Transcription Factors - genetics Kruppel-Like Transcription Factors - metabolism LIM Domain Proteins Metalloproteins - genetics Metalloproteins - metabolism Proto-Oncogene Proteins Proto-Oncogene Proteins c-myb - genetics Proto-Oncogene Proteins c-myb - metabolism Stem Cells - cytology Stem Cells - metabolism |
| Title | c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/20686118 https://www.proquest.com/docview/814465500 |
| Volume | 116 |
| WOSCitedRecordID | wos000284599900001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LT-MwEB7xWBYusLQsj33IB8TNauy83NMKqq1W2rZwWFBvlWOPJQ6kpSkr-u-ZOM7uCXHgkkSWIiX22P5m5ht_AOfKFMaijHlBeJQnuVZca5FysheF1jiTezmfu1E-majptH8TuDlVoFW2a6JfqO3c1DHynmqO-oqiH4tHXotG1cnVoKCxCdsxIZnaqPPp_yRCEnvNVdqhFK9hUaicI0Tda1jhTWaALIXcNCFex5h-rxkevPMrP8F-AJnssrGKQ9jAsgPdy5Ic7Ic1u2Ce9unj6R3YuWqfdget-FsHPo5Dzr0Lt4Y_rAtWPS18doHhct1oK5CPfV-xIPRDd2SrVny8ifOyuWO_R0PBdGnZaHwtGT4H3m15BLfDn38Gv3gQY-AmkfmKWxenQmXWapsRCDCOJnZa2KjI4kjpiJqTpKirYMmF033Tz1DqyGHmRFSgLhL5GbbKeYknwBClFOiyNHYqEWiVy1RfYmRtHpPHLE6BtZ07o9-uMxi6xPlTNfvXvadw3AzQbNEcyjGTda0Lje3Z2y9_gT3PARCCy_QrbDua6PgNPpi_q_tq-d0bEV0nN-MXpjDRJw |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=c-myb+supports+erythropoiesis+through+the+transactivation+of+KLF1+and+LMO2+expression&rft.jtitle=Blood&rft.au=Bianchi%2C+Elisa&rft.au=Zini%2C+Roberta&rft.au=Salati%2C+Simona&rft.au=Tenedini%2C+Elena&rft.date=2010-11-25&rft.eissn=1528-0020&rft.volume=116&rft.issue=22&rft.spage=e99&rft_id=info:doi/10.1182%2Fblood-2009-08-238311&rft_id=info%3Apmid%2F20686118&rft_id=info%3Apmid%2F20686118&rft.externalDocID=20686118 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1528-0020&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1528-0020&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1528-0020&client=summon |