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Lab presentation

We focus our research on the control of gene expression in human cells by chromatin organization, components and modifications, with a focus on the linker histone. The linker histone in mammals, participating in nucleosome spacing and higher-order chromatin structure, is a family of different histone H1 subtypes, including 7 somatic variants. It is poorly understood why so many H1 variants exist and whether they have particular features relevant to its functionality.

Knock-out experiments have suggested that the different variants are redundant and one isoform can substitute for another, but slowly new reports including ours are suggesting specific roles for the H1 variants, including involvement in specific gene expression regulation, and differential distribution in the human genome.

In a second line of research, we use an HIV promoter model to investigate the influence of chromatin organization at the integration site on HIV expression, with a focus on the role of heterochromatin on the establishment of viral latency, and we search for therapies for reactivation.

Projects

Research Lines:

  • Whether human histone H1 variants have distinct properties and roles in chromatin organization, gene expression control and, ultimately, cell growth.
  • Whether H1 variants are distributed distinctively in the genome, or with specific participation in particular gene promoters, or interact with different nuclear components.
  • What is the participation of H1 variants in tumor progression and cell differentiation.
  • How the organization and compaction of chromatin at the integration site influences the transcriptional activity of the HIV promoter and leads to viral latency.
  • What are the molecular mechanisms involved in HIV reactivation from latency by newly identified drugs.

Lab people

Principal investigator

After graduating in Biology at Autonomous University of Barcelona (UAB) Albert Jordan
went on to do his Ph.D. (1992-95) in the laboratory of Drs Jordi Barbé and Isidre Gibert
at the Dept. Genetics and Microbiology, UAB, where he was a Lecturer afterwards
(1996-98). In the meantime he spent five consecutive summer periods in Dr Peter
Reichard’s laboratory at the Karolinska Institute, Stockholm.

He then moved to San Francisco to undertake his postdoctoral work in the group of Dr Eric Verdin at the Gladstone Institutes-UCSF (1999-2001), where he became interested in the role of
chromatin in human and viral gene expression control. In 2002 he got a Ramon y Cajal
appointment to join the group of Dr Miguel Beato at CRG (Barcelona) where he
became staff scientist afterwards. Later, in 2008, he got a permanent CSIC position to
start an independent group at IBMB, Dept. Molecular Genomics.

He has been Department director on 2011-13 and 2015-19. In parallel, Dr Jordan has been
appointed coordinator of the Molecular Biology section of the Catalan Society of
Biology (SCB) between 2009-16, coordinator of the Chromatin and Epigenetics section
since 2017, and member of the Directive Committee of SCB (Sections Coordinator,
Secretary) since 2012. Dr Jordan has been awarded several public and private grants,
directed 9 PhD thesis and published more than 45 papers.

Past students

Alberto Bustillos

PhD Student

Andrea Izquierdo

PhD Student

Erik Abner

PhD Student

Lluís Millan

PhD Student

Edurne Gallastegui

PhD Student

Selected publications

Abner E, Jordan A (2019) HIV ‘shock and kill’ therapy: in need of revision. Antiviral Research 166: 19-34. doi: 10.1016/j.antiviral.2019.03.008.


AbnerE, StoszkoM, ZengL, ChenH-C, Izquierdo-BouldstridgeA, KonumaT, ZoritaE, FanunzaE, ZhangQ, MahmoudiT, ZhouM-M, FilionG, JordanA (2018) A new quinoline BRD4 inhibitor targets a distinctlatent HIV-1 reservoirfor re-activationfromother ‘shock’ drugs. Journal of Virology2018 Apr 27;92(10). pii: e02056-17.


Izquierdo-BouldstridgeA*, BustillosA*, Bonet-Costa C, Aribau P, Garcia D, Dabad M, Esteve-Codina A, Pascual L, Peiro S, Esteller M, Murtha M, Millán-AriñoLl, JordanA (2017)Histone H1 depletiontriggersaninterferon response in cancercellsviaactivation of heterochromaticrepeats. NucleicAcidsResearch45(20): 11622-42.


Millán-Ariño Ll, Izquierdo-Bouldstridge A, Jordan A (2016) Specificities and genomicdistribution of somaticmammalianhistone H1 subtypes. BBA Gene RegulatoryMechanisms 1859(3): 510-19.


MayorR*, Izquierdo-BouldstridgeA*, Millán-AriñoLl, BustillosA, SampaioC, LuqueN, JordanA (2015)Genomedistribution of replication-independenthistone H1 variants shows H1.0 associatedwithnucleolardomains and H1X associatedwith RNA polymerase II-enrichedregions. Journal of BiologicalChemistry 290(12):7474-91.


Millán-Ariño Ll, Islam A, Izquierdo-Bouldstridge A, Mayor R, Terme JM, Luque N, Sancho M, López-Bigas N, Jordan A (2014)Mapping of sixsomaticlinkerhistone H1 variants in human breastcancercellsuncoversspecificfeatures of H1.2. NucleicAcidsResearch 42:4474-4493.


Gallastegui E, MarshallB, VidalD, Sanchez-DuffhuesG, ColladoJA, Alvarez-FernándezC, LuqueN, TermeJM, GatellJM, Sánchez-PalominoS, MuñozE, MestresJ, Verdin E, Jordan A (2012) Combination of biologicalscreening in a cellularmodel of viral latencywith virtual screeningidentifies novel compoundsthatreactivate HIV-1. Journal of Virology86(7):3795-3808.


Terme JM*, Sesé B*, Millán-Ariño L, Mayor R, Izpisua-Belmonte JC, Barrero MJ, Jordan A (2011) Histone H1 variants are differentiallyexpressed and incorporatedintochromatinduringdifferentiation and reprogrammingtopluripotency. Journal of BiologicalChemistry 286(41):35347-57.


Gallastegui E, Millán-Zambrano G, Terme JM, Chávez S, Jordan A (2011) Chromatinreassemblyfactors are involved in transcriptionalinterferencepromoting HIV latency. Journal of Virology 85(7):3187-202.


Sancho M, Diani E, Beato M, Jordan A (2008) Depletion of human histone H1 variantsuncoversspecific roles in gene expression and cellgrowth. PLOS Genetics 2008 Oct;4(10):e1000227.


Subtil-Rodríguez A, Millán-Ariño L, Quiles I, Ballaré C, Beato M, Jordan A (2008) Progesteroneinduction of 11ß-hydroxysteroid dehydrogenasetype 2 promoter in breastcancercellsinvolvescoordinatedrecruitment of STAT5A and PR to a distal enhancer and polymerase tracking. Molecular and CellularBiology 28: 3830-3849.


Vicent GP, Ballaré C, Nacht AS, Clausell J, Subtil-Rodríguez A, Quiles I, Jordan A, Beato M. (2006) Induction of progesterone target genes requiresactivation of Erk and Mskkinases and phosphorylation of histone H3. Molecular Cell 24: 367-381.


Larsson KM, Jordan A, Eliasson R, Reichard P, Logan DT, Nordlund P (2004) Structuralmechanisms of allostericsubstratespecificityregulation in a ribonucleotidereductase. NatureStructure and Molecular Biology 11: 1142-1149.


Jordan A, Bisgrove D, Verdin E. (2003) HIV reproduciblyestablishes a latentinfectionafteracuteinfection of T cells in vitro. EMBO Journal 22: 1868-1877.


Jordan A, Defechereux P, Verdin E (2001) Thesite of HIV-1 integration in the human genome determines basal transcriptionalactivity and response toTattransactivator. EMBO Journal 20: 1726-1738.


Jordan A, Reichard P. (1998)Ribonucleotidereductases. Annual Reviews of Biochemistry67: 71-98.


Jordan A, Torrents E, Jeanthon C, Eliasson R, Hellman U, Wernstedt C, Barbé J, Gibert I, Reichard, P. (1997) B12-dependent ribonucleotidereductases from deeply rooted eubacteria are stucturally related to the aerobic enzyme from Escherichia coli. Proceedings of the National Academy of Sciences USA94: 13487-13492.


Jordan A, Pontis E, Atta M, Krrok M, Gibert I, Barbé J, Reichard P. (1994) A second class I ribonucleotidereductase in Enterobacteriaceae: characterization of the Salmonella typhimurium enzyme.Proceedings of the National Academy of Sciences USA91: 12892-12896.


For a complete list of A. Jordanpublications, searchPubMedfor:

(jordan a and bonet-costa c ) or (jordan a and izquierdo-bouldstridgea) or (jordan a and bartrons r) or (jordan a and termejm) or (jordan a and chavez s) or (jordan a and beato m) or (jordan a and verdin e) or (jordan a and reichard p) or (jordan a and gibert i) or (jordan a and uhlin u) or (jordan a and eklund h) or (valles aj) or (jordan a and biochimbiophys acta) or (jordan a and bachs o) or (jordan a and langley e) or (jordan a and abner e)

All publications

Abner E, Jordan A (2019) HIV ‘shock and kill’ therapy: in need of revision. Antiviral Research 166: 19-34. doi: 10.1016/j.antiviral.2019.03.008.


Salmerón-Hernández A, Noriega-Reyes MY, Jordan A, Baranda-Avila N, Langley E (2019) BCAS2 EnhancesCarcinogenicEffects of Estrogen Receptor Alpha in BreastCancerCells. International Journal of Molecular Sciences Feb 22;20(4). pii: E966. doi: 10.3390/ijms20040966


CarbonellA, FueyoR, Izquierdo-BouldstridgeA, MoretaC, Jordan A (2018) Epigeneticmechanisms in health and disease: BCEC 2017. Epigenetics13(3): 331-341. doi: 10.1080/15592294.2018.1434391.


AbnerE, StoszkoM, ZengL, ChenH-C, Izquierdo-BouldstridgeA, KonumaT, ZoritaE, FanunzaE, ZhangQ, MahmoudiT, ZhouM-M, FilionG, JordanA (2018) A new quinoline BRD4 inhibitor targets a distinctlatent HIV-1 reservoirfor re-activationfromother ‘shock’ drugs. Journal of Virology2018 Apr 27;92(10). pii: e02056-17.


Izquierdo-BouldstridgeA*, BustillosA*, Bonet-Costa C, Aribau P, Garcia D, Dabad M, Esteve-Codina A, Pascual L, Peiro S, Esteller M, Murtha M, Millán-AriñoLl, JordanA (2017)Histone H1 depletiontriggersaninterferon response in cancercellsviaactivation of heterochromaticrepeats. NucleicAcidsResearch45(20): 11622-42.


Perearnau A, Orlando S, Islam A, Gallastegui E, Martínez J, Jordan A, Bigas A, Aligué R, Pujol MJ, Bachs O (2017) p27Kip1, PCAF and PAX5 cooperate in thetranscriptionalregulation of specific target genes. NucleicAcidsResearch45(9):5086-99.


Castaño J, Morera C, Sesé B, BoueS, Bonet-CostaC, MartiM, RoqueA, Jordan A, BarreroMJ (2016) SETD7 regulatesthedifferentiation of human embryonicstemcells. PLOS Onedoi: 10.1371/journal.pone.0149502.

Jordan A (2016) Editorial-Histone H1 in gene expression and development. BBA Gene RegulatoryMechanisms 1859(3): 429-30.


Millán-Ariño Ll, Izquierdo-Bouldstridge A, Jordan A (2016) Specificities and genomicdistribution of somaticmammalianhistone H1 subtypes. BBA Gene RegulatoryMechanisms 1859(3): 510-19.


Noriega-Reyes MY, Rivas-Torres MA, Oñate-Ocaña LF, Jordan-Vallés A, Baranda-Avila N, Langley E (2015) Novel role for PINX1 as a coregulator of nuclear hormone receptors. Molecular and CellularEndocrinology 414: 9-18.


MayorR*, Izquierdo-BouldstridgeA*, Millán-AriñoLl, BustillosA, SampaioC, LuqueN, JordanA (2015)Genomedistribution of replication-independenthistone H1 variants shows H1.0 associatedwithnucleolardomains and H1X associatedwith RNA polymerase II-enrichedregions. Journal of BiologicalChemistry 290(12):7474-91.


Terme JM, Millán-AriñoLl, MayorR, LuqueN, Izquierdo-BouldstridgeA, BustillosA, SampaioC, CanesJ, FontI, SimaN, SanchoM, TorrenteL, ForcalesS, RoqueA, SuauP, JordanA (2014) Dynamics and dispensability of variant-specifichistone H1 Lys-26/Ser-27 and Thr-165 post-translationalmodifications. FEBS Letters 588(14):2353-62.


Millán-Ariño Ll, Islam A, Izquierdo-Bouldstridge A, Mayor R, Terme JM, Luque N, Sancho M, López-Bigas N, Jordan A (2014)Mapping of sixsomaticlinkerhistone H1 variants in human breastcancercellsuncoversspecificfeatures of H1.2. NucleicAcidsResearch 42:4474-4493.


Gallastegui E, MarshallB, VidalD, Sanchez-DuffhuesG, ColladoJA, Alvarez-FernándezC, LuqueN, TermeJM, GatellJM, Sánchez-PalominoS, MuñozE, MestresJ, Verdin E, Jordan A (2012) Combination of biologicalscreening in a cellularmodel of viral latencywith virtual screeningidentifies novel compoundsthatreactivate HIV-1. Journal of Virology86(7):3795-3808.
Novellasdemunt L, Obach M, Millán-Ariño Ll, Manzano A, Ventura F, Rosa JL, Jordan A, Navarro-Sabate A, Bartrons R (2012) Progestinsactivate 6-Phosphofructo-2-kinase/Fructose-2,6-Bisphosphatase (PFKFB3) in breastcancercells. BiochemicalJournal 442(2):345-56.


Terme JM*, Sesé B*, Millán-Ariño L, Mayor R, Izpisua-Belmonte JC, Barrero MJ, Jordan A (2011) Histone H1 variants are differentiallyexpressed and incorporatedintochromatinduringdifferentiation and reprogrammingtopluripotency. Journal of BiologicalChemistry 286(41):35347-57.


Gallastegui E, Millán-Zambrano G, Terme JM, Chávez S, Jordan A (2011) Chromatinreassemblyfactors are involved in transcriptionalinterferencepromoting HIV latency. Journal of Virology 85(7):3187-202.


Terme JM, Calvignac S, DucDodon M, Gazzolo L, Jordan A (2009) E box motifs as mediators of provirallatency of human retroviruses. Retrovirology 6: 81.


Quiles I, Millán-Ariño L, Subtil-Rodríguez A, Miñana B, Spinedi N, Ballaré C, Beato M, Jordan A (2009) Mutationalanalysis of progesterone receptor functionaldomains in stablecelllinesdelineates sets of genes regulatedbydifferentmechanisms. Molecular Endocrinology 23: 809-26.


Vanti M*, Gallastegui E*, Respaldiza I, Rodríguez-Gil A, Gómez-Herreros F, Jimeno-González S, Jordan A and Chávez S (2009) Yeastgeneticanalysisrevealstheinvolvement of chromatinreassemblyfactors in repressing HIV-1 basal transcription. PLOS Genetics 2009 Jan;5(1):e1000339.


Sancho M, Diani E, Beato M, Jordan A (2008) Depletion of human histone H1 variantsuncoversspecific roles in gene expression and cellgrowth. PLOS Genetics 2008 Oct;4(10):e1000227.


Subtil-Rodríguez A, Millán-Ariño L, Quiles I, Ballaré C, Beato M, Jordan A (2008) Progesteroneinduction of 11ß-hydroxysteroid dehydrogenasetype 2 promoter in breastcancercellsinvolvescoordinatedrecruitment of STAT5A and PR to a distal enhancer and polymerase tracking. Molecular and CellularBiology 28: 3830-3849.


Vicent GP, Ballaré C, Nacht AS, Clausell J, Subtil-Rodríguez A, Quiles I, Jordan A, Beato M (2008) Convergenceonchromatin of non-genomic and genomicpathways of hormone signaling. Journal of SteroidBiochemistry and Molecular Biology109: 344-349.


Vicent GP, Ballaré C, Nacht AS, Clausell J, Subtil-Rodríguez A, Quiles I, Jordan A, Beato M. (2006) Induction of progesterone target genes requiresactivation of Erk and Mskkinases and phosphorylation of histone H3. Molecular Cell 24: 367-381.


Larsson KM, Jordan A, Eliasson R, Reichard P, Logan DT, Nordlund P (2004) Structuralmechanisms of allostericsubstratespecificityregulation in a ribonucleotidereductase. NatureStructure and Molecular Biology 11: 1142-1149.


Jordan A, Bisgrove D, Verdin E. (2003) HIV reproduciblyestablishes a latentinfectionafteracuteinfection of T cells in vitro. EMBO Journal 22: 1868-1877.


Pion M, Jordan A, Biancotto A, Dequiedt F, Gondois-Rey F, Rondeau S, Vigne R, Hejnar J, Verdin E, Hirsch I (2003) Transcriptionalsuppression of in vitro-integrated human immunodeficiency virus type 1 doesnotcorrelatewithproviral DNA methylation. Journal of Virology 77: 4025-4032.


Jordan A, Defechereux P, Verdin E (2001) Thesite of HIV-1 integration in the human genome determines basal transcriptionalactivity and response toTattransactivator. EMBO Journal 20: 1726-1738.


Jordan A, Torrents E, Sala I, Hellman U, Gibert I, Reichard, P (1999)Ribonucleotide reduction in Pseudomonas species: simultaneous presence of active enzymes from different classes. Journal of Bacteriology181: 3974-3980.


Eliasson R, Pontis E, Jordan A, Reichard P (1999) Allosteric control of three B12-dependent (class II) ribonucleotidereductases. Implication for the evolution of ribonucleotide reduction. Journal of Biological Chemistry274: 7182-7189.


Jordan A, Reichard P. (1998)Ribonucleotidereductases. Annual Reviews of Biochemistry67: 71-98.


Fieschi F, Torrents E, Toulokhonova L, Jordan A, Hellman U, Gibert I, Barbé J, Karlsson M, Sjöberg B-M. (1998) The manganese-containing ribonucleotidereductase of Corynebacteriumammoniagenes is a class Ib enzyme. Journal of Biological Chemistry273: 4329-4337.


Jordan A, Torrents E, Jeanthon C, Eliasson R, Hellman U, Wernstedt C, Barbé J, Gibert I, Reichard, P. (1997) B12-dependent ribonucleotidereductases from deeply rooted eubacteria are stucturally related to the aerobic enzyme from Escherichia coli. Proceedings of the National Academy of Sciences USA94: 13487-13492.


Jordan A, Åslund F, Pontis E, Reichard P, Holmgren A. (1997) Characterization of E. coliNrdH: a glutaredoxin-like protein with thioredoxin-like activity profile. Journal of Biological Chemistry2: 18044-18050.


Eliasson R, Pontis E, Jordan A, Reichard P. (1996) Allosteric regulation of the third ribonucleotidereductase (NrdEF enzyme) from Enterobacteriaceae. Journal of Biological Chemistry 271: 26582-26587.


Jordan A, Pontis E, Åslund F, Hellman U, Gibert I, Reichard P. (1996) The ribonucleotidereductase system of Lactococcuslactis. Characterization of an NrdEF-enzyme and a new electron transport protein. Journal of Biological Chemistry27: 8779-8785.


Jordan A, Aragall E, Gibert I, Barbé J. (1996) Promoter identification and expression analysis of Salmonella typhimurium and Escherichia colinrdEF operons encoding one of two class I ribonucleotidereductases present in both bacteria. Molecular Microbiology19:777-790.


Jordan A, Pontis E, Atta M, Krrok M, Gibert I, Barbé J, Reichard P. (1994) A second class I ribonucleotidereductase in Enterobacteriaceae: characterization of the Salmonella typhimurium enzyme.Proceedings of the National Academy of Sciences USA91: 12892-12896.


Jordan A, Gibert I, Barbé J. (1994) Cloning and sequencing of the genes from S. typhimurium encoding a new bacterial ribonucleotidereductase. Journal of Bacteriology176: 3420-3427.

Project funding

Especificidad funcional de las variantes de la histona H1 humana:

  • AGENCY: Ministerio de Ciencia e Innovación – Plan Nacional BFU
  • PERIOD: 2018 – 2020
  • IP: Albert Jordan Vallès

Especificidad funcional de las variantes de la histona H1 humana.

  • AGENCY: Ministerio de Ciencia e Innovación – Plan Nacional BFU
  • PERIOD: 2015 – 2017
  • IP: Albert Jordan Vallès

Especificidad funcional de las variantes de la histona H1 humanas:

  • AGENCY: Ministerio de Ciencia e Innovación – Plan Nacional BFU
  • PERIOD: 2012 – 2014
  • IP: Albert Jordan Vallès

Determinantes genómicos del estado latente del VIH-1 y estrategias terapéuticas:

  • AGENCY: FIPSE
  • PERIOD: 2011 – 2013
  • IP: Albert Jordan Vallès

Estrategias terapéuticas para la reactivación del Virus de la Immunodeficiencia Humana en células latentes:

  • AGENCY: Fundación Eugenio Rodríguez Pascual
  • PERIOD: 2011
  • IP: Albert Jordan Vallès

Genómica estructural y aplicada:

  • AGENCY: AGAUR-DURSI – Grupos reconocidos
  • PERIOD: 2009 – 2013
  • IP: Joaquim Roca / Marian Martínez Balbas / Xavier de la Cruz / Albert Jordan

Especificidad de las variantes de la histona H1 humanas en la estructura de la cromatina, expresión génica y proliferación:

  • AGENCY: Ministerio de Ciencia e Innovación – Plan Nacional BFU
  • PERIOD: 2009 – 2011
  • IP: Albert Jordan Vallès

Reactivación del VIH en células T latentemente infectadas in vitro e in vivo:

  • AGENCY: FIPSE
  • PERIOD: 2006 – 2009
  • IP: Albert Jordan Vallès

Latencia del VIH. Estudio del mecanismo molecular y búsqueda de dianas para la reactivación:

  • AGENCY Instituto de Salud Carlos III – Fondo de Investigación Sanitaria
  • PERIOD: 2006 – 2008
  • IP: Albert Jordan Vallès

Regulación transcripcional y reorganización de la cromatina en los promotores pS2, 11 beta-HSD y MMTV en células de cáncer de mama en respuesta a hormonas esteroideas:

  • AGENCY: Ministerio de Ciencia y Tecnología – Plan Nacional SAF
  • PERIOD: 2002 – 2005
  • IP: Albert Jordan Vallès

Vacancies/Jobs

Candidates, send CV and an introductory letter (experience, references, motivation…) by email to albert.jordan@ibmb.csic.es

Pre- and post-doc candidates Chromatin regulation of human and viral gene expression

Pre- and post-doc candidates with an outstanding CV to apply to competitive fellowships will be always…

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Lab corner

A NEW QUINOLINE BRD4 INHIBITOR TARGETS A DISTINCT LATENT HIV-1 RESERVOIR FOR RE- ACTIVATION FROM OTHER ‘SHOCK’ DRUGS

Researchers of the IBMB have shown that a previously identified Human Immunodeficiency Virus (HIV) latency-reversing agent (MMQO) acts as a bromodomain inhibitor. Despite of very different chemical structures, MMQO mimics the action of JQ1, a well-known bromodomain inhibitor, and binds to the bromodomain and extraterminal domain (BET) family protein BRD4. Utilizing barcoded HIV-1minigenomes, we demonstrate that PKC pathway activators, HDAC and bromodomain inhibitors all target different subsets of proviral integrations. Considering the fundamental differences of these compounds and the synergies displayed between them, we propose that the field should concentrate on investigating the development of combinatory “shock” cocktail therapies for an improved reservoir reactivation aiming to eradicate the latent functional proportion of HIV-1 proviruses in a patient.

HISTONE H1 DEPLETION TRIGGERS AN INTERFERON RESPONSE IN CANCER CELLS

Researchers of the IBMB have shown that simultaneous depletion of particular histone H1 variants in human breast cancer cells triggers the cellular interferon response, originally designed to fight against invading pathogen-associated nucleic acids such as DNA or RNA viruses. They have shown that this is due to the derepression of heterochromatic non-coding RNAs such as satellites and endogenous retroviruses, which may be naturally repressed with the participation of particular histone H1 subtypes such as H1.2 and H1.4.

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