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 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 interactions
2021
The 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
2020
Cancer-specific mutation of GATA3 disrupts the transcriptional regulatory network governed by Estrogen Receptor alpha, FOXA1 and GATA3
Takaku M, Grimm S, De Kumar B, Bennett B, Wade P. Cancer-specific mutation of GATA3 disrupts the transcriptional regulatory network governed by Estrogen Receptor alpha, FOXA1 and GATA3. Nucleic Acids Research 2020, 48: 4756-4768. PMID: 32232341, PMCID: PMC7229857, DOI: 10.1093/nar/gkaa179.Peer-Reviewed Original ResearchConceptsRegulatory networksAltered chromatin architectureTranscriptional regulatory networksDifferential gene expressionEpithelial cell biologyTranscription factor FOXA1Mammary epithelial cellsEstrogen receptor alphaCancer-specific mutationsMammary gland developmentChromatin architectureChromatin localizationGenomic localizationReceptor alphaMutant cellsGenomic analysisNetwork downstreamGene setsCell biologyEstrogen receptorGene expressionGATA3 mutationsGland developmentSimilar mutationsFOXA1
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 acid
2016
The Methylation-Sensitive Enhancer Derare Maintains Hematopoietic Stem Cells through Regulation of Hoxb Cluster
Qian P, De Kumar B, Ahn Y, Nolte C, Paulson A, He X, Li Z, Perry J, Zhao M, Tao F, Krumlauf R, Li L. The Methylation-Sensitive Enhancer Derare Maintains Hematopoietic Stem Cells through Regulation of Hoxb Cluster. Blood 2016, 128: 725. DOI: 10.1182/blood.v128.22.725.725.Peer-Reviewed Original ResearchHematopoietic stem cellsHoxB gene expressionGene expressionLT-HSCsHOXB clusterHOXB cluster genesCluster genesHoxb genesCluster gene expressionChIP-seq analysisCis-regulatory elementsTrans-acting factorsFunctional hematopoietic stem cellsNext-generation sequencing technologiesStem cellsDNA methylation analysisCancer Genome Atlas (TCGA) projectHematopoietic cell typesLong-term reconstitution capacityHSC maintenancePutative enhancersTranscriptome analysisRegulatory networksRNA-seqGenetic regulatory networks
2013
Insights from transcriptional profiling the mouse hindbrain: Novel feedback between retinoids and Hox genes
Yurieva M, De Kumar B, Krumlauf R. Insights from transcriptional profiling the mouse hindbrain: Novel feedback between retinoids and Hox genes. The FASEB Journal 2013, 27: 966.1-966.1. DOI: 10.1096/fasebj.27.1_supplement.966.1.Peer-Reviewed Original ResearchHox genesTranscriptional profilingTranscription factorsDpc mouse embryosGene expression patternsKey transcription factorVertebrate hindbrainHindbrain patterningLaser capture microscopyHox familyFunctional validationMouse embryosExpression patternsGene expressionWild typeRhombomeresMouse hindbrainIndividual rhombomeresSingle rhombomereGenesNovel targetRetinoid metabolismHindbrainAnimal lethalityProfiling
2012
Poised RNA Polymerase II Changes over Developmental Time and Prepares Genes for Future Expression
Gaertner B, Johnston J, Chen K, Wallaschek N, Paulson A, Garruss A, Gaudenz K, De Kumar B, Krumlauf R, Zeitlinger J. Poised RNA Polymerase II Changes over Developmental Time and Prepares Genes for Future Expression. Cell Reports 2012, 2: 1670-1683. PMID: 23260668, PMCID: PMC3572839, DOI: 10.1016/j.celrep.2012.11.024.Peer-Reviewed Original ResearchConceptsPol IIMammalian embryonic stem cellsGenes de novoDevelopmental control genesPolycomb group repressionFuture gene expressionRNA Pol IIRNA polymerase IIEmbryonic stem cellsTissue-specific fashionChromatin stateDrosophila embryosPolymerase IIExtracellular signalsDevelopmental programStages of differentiationGene expressionControl genesDevelopmental timeSynchronous inductionDynamic expressionGenesStem cellsDe novoFuture expression
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