2024
The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response
Even Z, Meli A, Tyagi A, Vidyarthi A, Briggs N, de Kouchkovsky D, Kong Y, Wang Y, Waizman D, Rice T, De Kumar B, Wang X, Palm N, Craft J, Basu M, Ghosh S, Rothlin C. The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response. Immunity 2024, 57: 1893-1907.e6. PMID: 39096910, PMCID: PMC11421571, DOI: 10.1016/j.immuni.2024.07.006.Peer-Reviewed Original ResearchT cell receptorImmune responseNaive CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsIFN-IHelminth infectionsNippostrongylus brasiliensis infectionDecreased immune responseType I interferonNaive TT cellsMemory-likeUnrelated antigensTranscriptional changesExtracellular matrixSPF miceCell receptorsI interferonGerm-freeResponse to certain environmental cuesInfectionMiceFunctional changesCell transcriptional statesTranscriptional heterogeneityIntranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusThe chemokine receptor CXCR3 promotes CD8+ T cell–dependent lung pathology during influenza pathogenesis
Guo K, Yombo D, Wang Z, Navaeiseddighi Z, Xu J, Schmit T, Ahamad N, Tripathi J, De Kumar B, Mathur R, Hur J, Sun J, Olszewski M, Khan N. The chemokine receptor CXCR3 promotes CD8+ T cell–dependent lung pathology during influenza pathogenesis. Science Advances 2024, 10: eadj1120. PMID: 38170765, PMCID: PMC10776024, DOI: 10.1126/sciadv.adj1120.Peer-Reviewed Original ResearchConceptsLung pathologyT cellsLung injuryCytotoxic responsePeak viral loadChemokine receptor CXCR3Wild-type CD8Robust cytotoxic responseSingle-cell RNA sequencing analysisCXCR3 blockadeAdoptive transferEffector potentialT subpopulationsT effectorsViral clearanceViral loadEffector subsetsReceptor CXCR3Influenza pathogenesisCD8Therapeutic effectMurine lungInfluenza controlCentral memoryCXCR3Hox Genes
Duraiswamy A, Senkumar L, De Kumar B. Hox Genes. 2024 DOI: 10.1016/b978-0-12-822563-9.00196-7.Peer-Reviewed Original ResearchHox genesAberrant expression of HOX genesCell fate determinationExpression of Hox genesFate determinationTissue homeostasisMetastatic behavior of tumorsCell migrationGenesDevelopmental eventsDevelopmental defectsHoxCancer progressionAberrant expressionMetastatic behaviorBehavior of tumorsCellsDisease progressionDisease prognosisProteinHomeostasisOrganogenesisPrognosis
2023
Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding
Dastidar S, De Kumar B, Lauckner B, Parrello D, Perley D, Vlasenok M, Tyagi A, Koney N, Abbas A, Nechaev S. Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding. Nature Communications 2023, 14: 7420. PMID: 37973875, PMCID: PMC10654513, DOI: 10.1038/s41467-023-43157-7.Peer-Reviewed Original ResearchMultiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival
Sun Z, Zhang Z, Banu K, Gibson I, Colvin R, Yi Z, Zhang W, De Kumar B, Reghuvaran A, Pell J, Manes T, Djamali A, Gallon L, O'Connell P, He J, Pober J, Heeger P, Menon M. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. Journal Of Clinical Investigation 2023, 133: e170420. PMID: 37676733, PMCID: PMC10617779, DOI: 10.1172/jci170420.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossHuman leukocyte antigenExpression quantitative trait lociT cellsTGF-β1TGF-β1/Smad pathwayDonor-recipient differencesKidney allograft lossChronic allograft rejectionKidney transplant survivalDonor-recipient mismatchActive TGF-β1Allograft lossGraft lossAllograft rejectionTransplant cohortPeripheral bloodLeukocyte antigenClinical trialsImmune cellsHaplotype mismatchGenome-wide scaleTransplant survivalQuantitative trait lociSingle nucleotide polymorphism dataShared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube
Afzal Z, Lange J, Nolte C, McKinney S, Wood C, Paulson A, De Kumar B, Unruh J, Slaughter B, Krumlauf R. Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube. Development 2023, 150: dev201259. PMID: 37102683, PMCID: PMC10233718, DOI: 10.1242/dev.201259.Peer-Reviewed Original ResearchConceptsNascent transcriptionDynamic regulatory interactionsHox gene expressionCis-regulatory elementsRetinoic acid response elementMouse neural tubeTranscription of genesNon-coding RNAAcid response elementSingle-molecule fluorescentRetinoic acid responseMutant embryosHOXB clusterHox expressionAxial identityHoxb genesRegulatory interactionsTranscriptional mechanismsGene expressionDependent enhancersTranscriptionResponse elementResponsive enhancerNeural tubeCompetitive interactionsEnhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
Moriyama M, Lucas C, Monteiro V, Initiative Y, Iwasaki A, Chen N, Breban M, Hahn A, Pham K, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Vogels C, Grubaugh N. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221652120. PMID: 37036977, PMCID: PMC10120007, DOI: 10.1073/pnas.2221652120.Peer-Reviewed Original ResearchConceptsMHC-I expressionBreakthrough infectionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsMajor histocompatibility complex class I expressionCell-mediated immunityInfluenza virus infectionSARS-CoV-2 VOCsMHC-I upregulationClass I expressionSARS-CoV-2T cell recognitionVirus infectionMHC II expressionSpike proteinEnhanced inhibitionInfectionCell recognitionCommon mutationsReinfectionE proteinAntibodiesViral genesSubvariantsExpressionUtility of promoter hypermethylation in malignant risk stratification of intraductal papillary mucinous neoplasms
Chhoda A, Sharma A, Sailo B, Tang H, Ruzgar N, Tan W, Ying L, Khatri R, Narayanan A, Mane S, De Kumar B, Wood L, Iacobuzio-Donahue C, Wolfgang C, Kunstman J, Salem R, Farrell J, Ahuja N. Utility of promoter hypermethylation in malignant risk stratification of intraductal papillary mucinous neoplasms. Clinical Epigenetics 2023, 15: 28. PMID: 36803844, PMCID: PMC9942382, DOI: 10.1186/s13148-023-01429-5.Peer-Reviewed Original ResearchConceptsPapillary mucinous neoplasmMalignant risk stratificationCACNA1G geneRisk stratificationMucinous neoplasmsBiomarker panelBackgroundIntraductal papillary mucinous neoplasmIntraductal papillary mucinous neoplasmEarly detectionPrevious case-control studyHigh-grade dysplasiaCase-control studyPancreatic cancer precursorsReceiver Operating Characteristic (ROC) curve analysisSignificant diagnostic challengeCross-sectional imagingCharacteristic curve analysisOperating Characteristic curve analysisG geneHigh diagnostic specificityPrior validation studiesSignificant procedural riskIPMN tissuesSurgical resectionAdvanced neoplasiaAge-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose
Filardi B, Monteiro V, Schwartzmann P, do Prado Martins V, Zucca L, Baiocchi G, Malik A, Silva J, Hahn A, Chen N, Pham K, Pérez-Then E, Miric M, Brache V, Cochon L, Larocca R, Della Rosa Mendez R, Silveira D, Pinto A, Croda J, Yildirim I, Omer S, Ko A, Vermund S, Grubaugh N, Iwasaki A, Lucas C, Initiative Y, Vogels C, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W. Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose. Science Translational Medicine 2023, 15: eade6023. PMID: 36791210, DOI: 10.1126/scitranslmed.ade6023.Peer-Reviewed Original ResearchConceptsBooster doseAntibody responseNeutralization titersVirus-specific IgG titersOlder adultsAntiviral humoral immunityPlasma antibody responsesHigh-risk populationSARS-CoV-2 spikeYears of ageAge-dependent impairmentHeterologous regimensBooster dosesBooster vaccineCoronaVac vaccineIgG titersProtective immunityHumoral immunityHumoral responseCoronaVacOmicron waveBooster strategyAge groupsEarly controlVaccineAccelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection
Chaguza C, Hahn A, Petrone M, Zhou S, Ferguson D, Breban M, Pham K, Peña-Hernández M, Castaldi C, Hill V, Initiative Y, Billig K, Earnest R, Fauver J, Kalinch C, Kerantzas N, Koch T, De Kumar B, Landry M, Ott I, Peaper D, Tikhonova I, Vogels C, Schulz W, Swanstrom R, Roberts S, Grubaugh N. Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection. Cell Reports Medicine 2023, 4: 100943. PMID: 36791724, PMCID: PMC9906997, DOI: 10.1016/j.xcrm.2023.100943.Peer-Reviewed Original ResearchConceptsChronic infectionEvolutionary ratesGenetic diversityIntrahost evolutionDistinct genotypesHigher viral genome copiesVirus evolutionary ratesSARS-CoV-2 evolutionUntreated chronic infectionAdvantageous mutationsNucleotide substitutionsViral genome copiesDivergent variantsInfection hypothesisVariant emergenceViral populationsInfectious virusInfectionHallmark changesGenome copiesDifferent genotypesDiversityGenotypesTemporal dynamicsEvolutionDNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ
Pramio D, Vieceli F, Varella-Branco E, Goes C, Kobayashi G, da Silva Pelegrina D, de Moraes B, El Allam A, De Kumar B, Jara G, Farfel J, Bennett D, Kundu S, Viapiano M, Reis E, de Oliveira P, Dos Santos E Passos-Bueno M, Rothlin C, Ghosh S, Schechtman D. DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ. Biochimica Et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 2023, 1866: 194909. PMID: 36682583, PMCID: PMC10037092, DOI: 10.1016/j.bbagrm.2023.194909.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsInternal promoterNeuronal differentiationEpigenetic mechanismsDNA methylationUpstream promoterProtein kinase C ζHuman neuronal differentiationSite-specific hypermethylationAberrant DNA hypermethylationPluripotent stem cellsEpigenetic regulationSame epigenetic mechanismsLong-term memory formationDNA hypermethylationDemethylated regionsEpigenetic factorsPromoter regionTissue specificityMolecular mechanismsPRKCZ geneDifferentiated neuronsPromoterProtein kinase M zetaLong-term potentiation
2022
Cellular Heterogeneity and Molecular Reprogramming of the Host Response during Influenza Acute Lung Injury
Guo K, Yombo D, Schmit T, Wang Z, Navaeiseddighi Z, Sathish V, Mathur R, Wu M, De Kumar B, Hur J, Khan N. Cellular Heterogeneity and Molecular Reprogramming of the Host Response during Influenza Acute Lung Injury. Journal Of Virology 2022, 96: e01246-22. PMID: 36286482, PMCID: PMC9645213, DOI: 10.1128/jvi.01246-22.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryIAV infectionHost responseDysregulated host responseExuberant host responseOutcome of interferonTotal immune cellsMonocyte-derived macrophagesSingle-cell RNA sequencing analysisChemokine responsesAcute injuryCellular levelImmune cellsNonimmune cellsBarrier integrityMyeloid cellsTherapeutic interventionsCellular heterogeneityInjuryChemokine signalingNonhematopoietic cellsInfectionRNA sequencing analysisMechanistic associationRapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Chaguza C, Coppi A, Earnest R, Ferguson D, Kerantzas N, Warner F, Young HP, Breban MI, Billig K, Koch RT, Pham K, Kalinich CC, Ott IM, Fauver JR, Hahn AM, Tikhonova IR, Castaldi C, De Kumar B, Pettker CM, Warren JL, Weinberger DM, Landry ML, Peaper DR, Schulz W, Vogels CBF, Grubaugh ND. Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons. Med 2022, 3: 325-334.e4. PMID: 35399324, PMCID: PMC8983481, DOI: 10.1016/j.medj.2022.03.010.Peer-Reviewed Original ResearchConceptsSpike gene target failureSARS-CoV-2 Omicron variantPositivity rateOmicron variantOmicron infectionVaccine dosesVaccine-induced immunityNumber of dosesTest positivity rateOdds of infectionSARS-CoV-2Significant reductionDominant Delta variantUnvaccinated personsVaccination statusHigher oddsDelta variantInfectionVaccine manufacturersDisease controlVirus copiesDosesPCR testOddsTarget failureComparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA
Earnest R, Uddin R, Matluk N, Renzette N, Turbett SE, Siddle KJ, Loreth C, Adams G, Tomkins-Tinch CH, Petrone ME, Rothman JE, Breban MI, Koch RT, Billig K, Fauver JR, Vogels CBF, Bilguvar K, De Kumar B, Landry ML, Peaper DR, Kelly K, Omerza G, Grieser H, Meak S, Martha J, Dewey HB, Kales S, Berenzy D, Carpenter-Azevedo K, King E, Huard RC, Novitsky V, Howison M, Darpolor J, Manne A, Kantor R, Smole SC, Brown CM, Fink T, Lang AS, Gallagher GR, Pitzer VE, Sabeti PC, Gabriel S, MacInnis BL, Team N, Altajar A, DeJesus A, Brito A, Watkins A, Muyombwe A, Blumenstiel B, Neal C, Kalinich C, Liu C, Loreth C, Castaldi C, Pearson C, Bernard C, Nolet C, Ferguson D, Buzby E, Laszlo E, Reagan F, Vicente G, Rooke H, Munger H, Johnson H, Tikhonova I, Ott I, Razeq J, Meldrim J, Brown J, Wang J, Vostok J, Beauchamp J, Grimsby J, Hall J, Messer K, Larkin K, Vernest K, Madoff L, Green L, Webber L, Gagne L, Ulcena M, Ray M, Fisher M, Barter M, Lee M, DeFelice M, Cipicchio M, Smith N, Lennon N, Fitzgerald N, Kerantzas N, Hui P, Harrington R, Downing R, Haye R, Lynch R, Anderson S, Hennigan S, English S, Cofsky S, Clancy S, Mane S, Ash S, Baez S, Fleming S, Murphy S, Chaluvadi S, Alpert T, Rivard T, Schulz W, Mandese Z, Tewhey R, Adams M, Park D, Lemieux J, Grubaugh N. Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA. Cell Reports Medicine 2022, 3: 100583. PMID: 35480627, PMCID: PMC8913280, DOI: 10.1016/j.xcrm.2022.100583.Peer-Reviewed Original ResearchConceptsEnhanced transmissibilitySARS-CoV-2 variant DeltaSARS-CoV-2 Delta variantViral RNA copiesPublic health programsAlpha infectionDelta infectionEffective reproductive numberDelta variantHealth programsVariant DeltaRNA copiesInfectionAlphaReproductive numberTransmissibilityEpidemiological dynamicsAssessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents
Oliveira CR, Niccolai LM, Sheikha H, Elmansy L, Kalinich CC, Grubaugh ND, Shapiro ED, Billig K, Breban M, Brito A, Earnest R, Fauver J, Koch T, Ott I, Petrone M, Vogels C, Pham K, Tikhonova I, Castaldi C, Mane S, Bilguvar K, De Kumar B, Ferguson D, Kerantzas N, Landry M, Peaper D, Schulz W. Assessment of Clinical Effectiveness of BNT162b2 COVID-19 Vaccine in US Adolescents. JAMA Network Open 2022, 5: e220935. PMID: 35238933, PMCID: PMC8895259, DOI: 10.1001/jamanetworkopen.2022.0935.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionCase-control studyVaccine effectivenessBNT162b2 vaccineSARS-CoV-2Medical recordsAsymptomatic SARS-CoV-2 infectionBNT162b2 COVID-19 vaccineRetrospective case-control studyRT-PCR test resultsSARS-CoV-2 testUS adolescentsReverse transcription polymerase chain reaction testConditional logistic regression modelsTranscription polymerase chain reaction testDoses of vaccineControl participantsClinical trial populationsRelevant clinical dataCase participantsCOVID-19 vaccinePositive test resultsChain reaction testCounty of residenceNegative test results
2021
Analysis of lamprey meis genes reveals that conserved inputs from Hox, Meis and Pbx proteins control their expression in the hindbrain and neural tube
Parker H, De Kumar B, Pushel I, Bronner M, Krumlauf R. Analysis of lamprey meis genes reveals that conserved inputs from Hox, Meis and Pbx proteins control their expression in the hindbrain and neural tube. Developmental Biology 2021, 479: 61-76. PMID: 34310923, DOI: 10.1016/j.ydbio.2021.07.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBody PatterningConserved SequenceEnhancer Elements, GeneticGene ExpressionGene Expression Regulation, DevelopmentalGenes, HomeoboxHomeodomain ProteinsLampreysMyeloid Ecotropic Viral Integration Site 1 ProteinNeural CrestNeural TubePre-B-Cell Leukemia Transcription Factor 1RhombencephalonTranscription FactorsConceptsMeis genesTALE proteinsDivergence of jawedSea lamprey genomeEvolution of vertebratesNeural crest cellsLamprey genomeTALE factorsPattern of expressionPbx proteinsJawed vertebratesVertebrate evolutionDeep ancestryJawless vertebratesLamprey embryosRhombomeric domainsTransgenic reporterNeural enhancerSimilar relative positionsRegulatory interactionsPharyngeal archesReporter expressionHead developmentCrest cellsSequence alignmentAutocrine GMCSF Signaling Contributes to Growth of HER2+ Breast Leptomeningeal CarcinomatosisGMCSF Contributes to Breast Leptomeningeal Carcinomatosis
Ansari K, Bhan A, Saotome M, Tyagi A, De Kumar B, Chen C, Takaku M, Jandial R. Autocrine GMCSF Signaling Contributes to Growth of HER2+ Breast Leptomeningeal CarcinomatosisGMCSF Contributes to Breast Leptomeningeal Carcinomatosis. Cancer Research 2021, 81: 4723-4735. PMID: 34247146, PMCID: PMC8986153, DOI: 10.1158/0008-5472.can-21-0259.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutocrine CommunicationBreast NeoplasmsCell Line, TumorCell ProliferationCell SurvivalDisease Models, AnimalGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorHumansMeningeal CarcinomatosisMiceOncogene ProteinsProtein Kinase InhibitorsReceptor, ErbB-2Signal TransductionXenograft Model Antitumor AssaysConceptsOligodendrocyte progenitor cellsLeptomeningeal carcinomatosisLC growthPan-Aurora kinase inhibitorKinase inhibitorsSuppression of HER2Growth of HER2Central nervous system cell typesProliferation of HER2Nervous system cell typesBreast cancer cellsPrimary HER2Targetable axisOminous complicationIntrathecal deliveryMolecular mechanismsTreatment optionsDire prognosisSpinal cordBreast cancerHER2LC developmentLeptomeningesLC/MS-MSCarcinomatosisThe Hox protein conundrum: The “specifics” of DNA binding for Hox proteins and their partners
De Kumar B, Darland D. The Hox protein conundrum: The “specifics” of DNA binding for Hox proteins and their partners. Developmental Biology 2021, 477: 284-292. PMID: 34102167, PMCID: PMC8846413, DOI: 10.1016/j.ydbio.2021.06.002.Peer-Reviewed Original ResearchConceptsProtein binding specificityHox proteinsAnterior-posterior body axisTranscription factor-DNA interactionsBinding specificityHox protein functionMulti-protein interactionsHomeodomain transcription factorHomeotic genesSegmental identityUnique target specificityProtein functionTranscription factorsCooperative binding modelGene expressionBody axisMolecular characterizationTarget specificityProteinDNAMouse systemRecent studiesSubsequent alterationDrosophilaGenesGenome-Wide Binding Analyses of HOXB1 Revealed a Novel DNA Binding Motif Associated with Gene Repression
Singh N, De Kumar B, Paulson A, Parrish M, Scott C, Zhang Y, Florens L, Krumlauf R. Genome-Wide Binding Analyses of HOXB1 Revealed a Novel DNA Binding Motif Associated with Gene Repression. Journal Of Developmental Biology 2021, 9: 6. PMID: 33546292, PMCID: PMC7931043, DOI: 10.3390/jdb9010006.Peer-Reviewed Original ResearchHistone marksGenome-wide binding analysisRepressive histone marksActive histone marksTranscriptional repressor RESTExpression of Hoxb1Specific regulatory functionsEmbryonic stem cellsAnimal developmentGene repressionHoxb1 functionGene regulationNeural fateRepressor RESTRepressive roleTranscription factorsHoxb1Diverse DNATarget genesReporter geneGene expressionRegulatory functionsStem cellsMotifBinding analysis