2023
Shared 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 ResearchMeSH KeywordsAnimalsEnhancer Elements, GeneticHomeodomain ProteinsIn Situ Hybridization, FluorescenceMiceMice, TransgenicNeural TubeTretinoinConceptsNascent 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 interactions
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 alignmentThe 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 ResearchMeSH KeywordsAnimalsDNADNA-Binding ProteinsGenes, HomeoboxHomeodomain ProteinsHumansModels, GeneticProtein BindingConceptsProtein 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 alterationDrosophilaGenes
2020
A six-amino-acid motif is a major determinant in functional evolution of HOX1 proteins
Singh N, De Kumar B, Paulson A, Parrish M, Zhang Y, Florens L, Conaway J, Si K, Krumlauf R. A six-amino-acid motif is a major determinant in functional evolution of HOX1 proteins. Genes & Development 2020, 34: 1680-1696. PMID: 33184220, PMCID: PMC7706710, DOI: 10.1101/gad.342329.120.Peer-Reviewed Original ResearchConceptsC-terminal motifAncestral activityFunctional analysisDNA-binding patternsGenome-wide analysisDNA-binding regionLow sequence similarityDNA-binding experimentsAmino acid sequenceSix-amino acid motifAncestral functionPbx proteinsEvolutionary noveltyGene duplicationFunctional diversificationHoxa1 proteinMouse proteinProtein functionSequence similarityFunctional evolutionAcid sequenceChimeric proteinMouse cellsHoxb1Structural predictions
2019
Hox genes: Downstream “effectors” of retinoic acid signaling in vertebrate embryogenesis
Nolte C, De Kumar B, Krumlauf R. Hox genes: Downstream “effectors” of retinoic acid signaling in vertebrate embryogenesis. Genesis 2019, 57: e23306. PMID: 31111645, DOI: 10.1002/dvg.23306.Peer-Reviewed Original ResearchConceptsHox genesAxial patterningHox gene expressionAnteroposterior axisBasic body planGene regulatory networksVertebrate embryogenesisAnimal developmentPatterning of cellsVertebrate developmentBody planAxial specificationRegulatory networksCombinatorial codeTissue contextGene expressionDirect effectorVertebrate planHematopoietic systemGenesReproductive organsRegulatory processesEmbryogenesisDifferential responseRetinoic acidA Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates
Parker H, De Kumar B, Green S, Prummel K, Hess C, Kaufman C, Mosimann C, Wiedemann L, Bronner M, Krumlauf R. A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates. Nature Communications 2019, 10: 1189. PMID: 30867425, PMCID: PMC6416258, DOI: 10.1038/s41467-019-09197-8.Peer-Reviewed Original ResearchConceptsNeural crestHox genesAncestral mechanismRegulatory circuitsUpstream regulatory componentsNeural crest patterningAncient paraloguesPbx proteinsJawed vertebratesAncient conservationExtant vertebratesAncestral activityRegulatory interactionsHOX2 genesRegulatory componentsVertebratesJaw formationGenesGnathostomesEnhancerHoxLampreyParaloguesImportant roleHoxa2
2018
Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis
Qian P, De Kumar B, He X, Nolte C, Gogol M, Ahn Y, Chen S, Li Z, Xu H, Perry J, Hu D, Tao F, Zhao M, Han Y, Hall K, Peak A, Paulson A, Zhao C, Venkatraman A, Box A, Perera A, Haug J, Parmely T, Li H, Krumlauf R, Li L. Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis. Cell Stem Cell 2018, 22: 740-754.e7. PMID: 29727682, DOI: 10.1016/j.stem.2018.04.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnhancer Elements, GeneticEpigenesis, GeneticHEK293 CellsHematopoiesisHomeodomain ProteinsHumansMiceMice, Inbred C57BLMice, KnockoutRetinoidsConceptsHoxb expressionHematopoietic stem cellsDNA methylationCoordinate regulationLoss of HSCsCis-regulatory elementsSpecific DNA methylationDNA methylome analysisHox genesHOXB clusterHox expressionEpigenetic regulationDNA methyltransferasesMethylome analysisHoxb genesCluster expressionLT-HSCsRetinoid signalingNormal hematopoiesisGenesStem cellsLeukemogenesisMethylationReconstitution capacityRegulation
2017
Hoxa1 targets signaling pathways during neural differentiation of ES cells and mouse embryogenesis
De Kumar B, Parker H, Paulson A, Parrish M, Zeitlinger J, Krumlauf R. Hoxa1 targets signaling pathways during neural differentiation of ES cells and mouse embryogenesis. Developmental Biology 2017, 432: 151-164. PMID: 28982536, DOI: 10.1016/j.ydbio.2017.09.033.Peer-Reviewed Original ResearchConceptsTarget genesEar developmentES cellsDifferential gene expression analysisGenome-wide analysisNeural crest specificationFunctional rolePutative target genesTransgenic mouse embryosMajor signaling pathwaysNeural crest migrationRelevant target genesDown-stream componentsMouse ES cellsGene expression analysisImportant functional roleRetinoic acidEvolutionary conservationEpigenetic marksHox cofactorsMutant phenotypeMouse embryogenesisNearby genesNeural fateMouse developmentHOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets
De Kumar B, Parker H, Paulson A, Parrish M, Pushel I, Singh N, Zhang Y, Slaughter B, Unruh J, Florens L, Zeitlinger J, Krumlauf R. HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets. Genome Research 2017, 27: 1501-1512. PMID: 28784834, PMCID: PMC5580710, DOI: 10.1101/gr.219386.116.Peer-Reviewed Original ResearchConceptsCross-regulatory interactionsTALE proteinsTALE membersCombinatorial binding patternsGenome-wide analysisGenome-wide basisCross-regulatory networkDiverse functional rolesMouse ES cellsHox cofactorsTALE familyFunctional diversityTransgenic reporterCombinatorial interactionsRegulatory networksHox-PbxProteomic analysisEnhancer activityHOXA1ES cellsFunctional roleProteinDistinct mechanismsBinding patternDistinct classes
2015
Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells
De Kumar B, Parrish M, Slaughter B, Unruh J, Gogol M, Seidel C, Paulson A, Li H, Gaudenz K, Peak A, McDowell W, Fleharty B, Ahn Y, Lin C, Smith E, Shilatifard A, Krumlauf R. Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells. Genome Research 2015, 25: 1229-1243. PMID: 26025802, PMCID: PMC4510006, DOI: 10.1101/gr.184978.114.Peer-Reviewed Original ResearchConceptsChromatin modificationsHomeotic clustersHox genesES cellsClustered Hox genesHomeotic gene transcriptionMouse embryonic stem cellsNoncoding RNA genesRetinoid-induced transcriptionGenome-wide approachesCis-regulatory elementsEmbryonic stem cellsTranscription stateChromatin marksHOXB clusterNoncoding genesRNA genesSegmental identityActive transcriptionNoncoding RNAsTranscription factorsEpigenetic profilesGene transcriptionEpigenetic changesBody axis
2014
Hox Complex Analysis Through BAC Recombineering
Parrish M, Ahn Y, Nolte C, De Kumar B, Krumlauf R. Hox Complex Analysis Through BAC Recombineering. Methods In Molecular Biology 2014, 1196: 59-87. PMID: 25151158, DOI: 10.1007/978-1-4939-1242-1_5.Peer-Reviewed Original Research
2011
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC)
Lin C, Garrett A, De Kumar B, Smith E, Gogol M, Seidel C, Krumlauf R, Shilatifard A. Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Genes & Development 2011, 25: 1486-1498. PMID: 21764852, PMCID: PMC3143939, DOI: 10.1101/gad.2059211.Peer-Reviewed Original ResearchConceptsSuper elongation complexEmbryonic stem cellsElongation complexPol IIDifferentiation signalsDynamic transcriptional eventsMurine embryonic stem cellsRNA polymerase IIStem cellsGlobal genomic analysisTranscription elongationPolymerase IITranscriptional regulationTranscriptional activationTranscriptional eventsGenomic analysisEnvironmental cuesES cellsGene expressionHuman cellsEnvironmental stimuliGenesEssential roleActivation signalsMajor classes