Axel Visel

Staff Scientist, Genomics Division

Lawrence Berkeley National Laboratory
MS84-171
1 Cyclotron Rd
Berkeley, CA 94720

Phone: 1-510-495-2301
Fax: 1-510-486-4229

e-mail: avisel@lbl.gov

Axel




Research Interests

The sequence of the human genome has been known for over a decade, but well-defined functional annotations exist mainly for the small portion of the genome that encodes proteins. In sharp contrast, the 98% non-coding regions of the genome remain incompletely annotated. Examples from gene-centric studies have provided strong evidence that the non-coding portion of the genome harbors distant-acting transcriptional enhancers and have shown that these regulatory sequences are critical for normal embryonic development. Human genetic studies also identified examples of human disease caused by perturbed enhancer sequences. However, systematic identification and functional characterization of distant-acting enhancers in the human genome continues to present a formidable challenge for several reasons:
  • In contrast to the genetic code of proteins, the sequence features of enhancers are poorly understood, impeding their reliable computational identification in the human genome.
  • Transcriptional enhancers can act over long distances (hundreds of thousands of basepairs) and can be located upstream, downstream or in introns of protein-coding genes. Their genomic position can therefore not be easily inferred from the known position and structure of a protein-coding gene.
  • Many genes are surrounded by complex arrays of regulatory elements with distinct and/or partially redundant activities.
  • The in vivo activity patterns of regulatory elements are difficult to predict by computational methods and generally transgenic reporter assays are required to establish with certainty when and where a particular regulatory sequence is active during development or in adult organs.
  • Various epigenomic features and molecular marks of regulatory sequences including enhancers have been identified through chromatin studies, yet it remains unclear how these insights can be leveraged to provide a complete functional annotation of in vivo activities of regulatory sequences genome-wide.

Fine Tuning of Facial Morphology with Enhancers - see Science 342:1241006
We are interested in combining comparative genomics, sequencing-based chromatin studies (ChIP-seq), and transgenic reporter assays to identify and characterize distant-acting transcriptional enhancers at a genomic scale. These studies provide genome-wide predictions of sequences that are likely to be enhancers, as well as experimental evidence for the in vivo function of subsets of these enhancer candidates. Our efforts focus in particular on the generation of experimental datasets that will be useful to elucidate fundamental mechanisms of development (e.g. forebrain, heart and craniofacial development) and reveal regulatory sequences that are relevant for related forms of human disease.
Postdoctoral Positions available (experimental and computational). For details, please inquire by e-mail.

Selected Publications

(for complete list, see below or PubMed)

Nord AS, ..., Rubenstein JL, Rubin EM, Pennacchio LA*, Visel A*. (14 authors). Rapid and Pervasive Changes in Genome-wide Enhancer Usage during Mammalian Development. Cell 2013, 155:1521-1531. PubMed
Attanasio C, Nord AS, Zhu Y, ..., Rubin EM, FitzPatrick DR, Ren B, Hallgrímsson B, Pennacchio LA, Visel A. (20 authors). Fine tuning of craniofacial morphology by distant-acting enhancers. Science 2013, 342:1241006. PubMed Free Full Text Free PDF
Visel A*, ..., Ovcharenko I, Pennacchio LA, Rubenstein JL. (25 authors). A High-Resolution Enhancer Atlas of the Developing Telencephalon. Cell 2013, 152:895-908 PubMed PMC Full Text PMC Free PDF
ENCODE Project Consortium. (400+ authors incl. Visel A). An integrated encyclopedia of DNA elements in the human genome. Nature 2012, 489:57-74. PubMed Open Access Full Text Open Access PDF
May D, ..., Simpson PC, Rubin EM, Black BL, Bristow J, Pennacchio LA*, Visel A*. (17 authors). Large-scale discovery of enhancers from human heart tissue. Nature Genet 2011, PubMed PMC Full Text PMC Free PDF
Blow MJ, ..., Ren B, Black BL, Rubin EM, Visel A*, Pennacchio LA* (17 authors). ChIP-seq Identification of Weakly Conserved Heart Enhancers. Nature Genet 2010, 42:806-10. PubMed News and Views PMC Full Text PMC Free PDF
Visel A, ..., Cohen JC, Rubin EM, Pennacchio LA (10 authors). Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature 2010, 464:409-412. PubMed PMC Full Text PMC Free PDF
Visel A, Rubin EM, Pennacchio LA. Genomic views of distant-acting enhancers (Review). Nature 2009, 461:199-205. PubMed PMC Full Text PMC Free PDF
Visel A*, Blow MJ*, ..., Ren B, Rubin EM, Pennacchio LA (14 authors). ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 2009, 457:854-858. PubMed PMC Full Text PMC Free PDF Data Sets
Prabhakar S, Visel A, ..., Pennacchio LA, Rubin EM, Noonan JP (13 authors). Human-specific gain of function in a developmental enhancer. Science 2008, 312:1346-50. PubMed PMC Full Text PMC Free PDF
Visel A, ..., Rubin EM, Pennacchio LA (10 authors). Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nature Genet 2008, 40:158-60. PubMed PMC Full Text PMC Free PDF Data Sets
Pennacchio LA, ..., Visel A, Rubin EM (19 authors). In vivo enhancer analysis of human conserved non-coding sequences. Nature 2006, 444(7118):499-502. PubMed



Databases

VISTA Enhancer Browser - activity of conserved developmental enhancers in transgenic mouse embryos at e11.5
Genepaint.org - ISH-based expression atlas of the e14.5 mouse embryo
Allen Brain Atlas - Genome-wide ISH-based high-resolution expression atlas of the adult mouse brain
FaceBase - A resource for craniofacial researchers



All Publications

Nord AS, Blow MJ, Attanasio C, Akiyama JA, Holt A, Hosseini R, Phouanenavong S, Plajzer-Frick I, Shoukry M, Afzal V, Rubenstein JL, Rubin EM, Pennacchio LA*, Visel A*. Rapid and Pervasive Changes in Genome-wide Enhancer Usage during Mammalian Development. Cell 2013, 155:1521-1531. PubMed
Attanasio C, Nord AS, Zhu Y, Blow MJ, Li Z, Liberton DK, Morrison H, Plajzer-Frick I, Holt A, Hosseini R, Phouanenavong S, Akiyama JA, Shoukry M, Afzal V, Rubin EM, FitzPatrick DR, Ren B, Hallgrímsson B, Pennacchio LA, Visel A. Fine tuning of craniofacial morphology by distant-acting enhancers. Science 2013, 342:1241006. PubMed Free Full Text Free PDF
Parker SC, Stitzel ML, Taylor DL, Orozco JM, Erdos MR, Akiyama JA, van Bueren KL, Chines PS, Narisu N; NISC Comparative Sequencing Program, Black BL, Visel A, Pennacchio LA, Collins FS. Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants. Proc Natl Acad Sci U S A 2013, 110:17921-6. PubMed Open Access Full Text Open Access PDF Open Access PDF with Supplementary Data
Sanchez-Castro M, Gordon CT, Petit F, Nord AS, Callier P, Andrieux J, Guérin P, Pichon O, David A, Abadie V, Bonnet D, Visel A, Pennacchio LA, Amiel J, Lyonnet S, Le Caignec C. Congenital Heart Defects in Patients with Deletions Upstream of SOX9. Human Mutat 2013, 34:1628-31 PubMed
Gross SM, Martin JA, Simpson J, Abraham-Juarez MJ, Wang Z, Visel A. De novo transcriptome assembly of drought tolerant CAM plants, Agave deserti and Agave tequilana. BMC Genomics 2013, 14:563. PubMed Open Access Full Text Open Access PDF Supplementary Files
Chen YJ, Vogt D, Wang Y, Visel A, Silberberg SN, Nicholas CR, Danjo T, Pollack JL, Pennacchio LA, Anderson S, Sasai Y, Baraban SC, Kriegstein AR, Alvarez-Buylla A, Rubenstein JL. Use of MGE enhancers for labeling and selection of embryonic stem cell-derived medial ganglionic eminence progenitors and neurons. PLoS One 2013, 8:e61956. PubMed Open Access Full Text Open Access PDF
Dickel DE, Visel A, Pennacchio LA. Functional anatomy of distant-acting mammalian enhancers. Philos Trans R Soc Lond B Biol Sci 2013, 368:20120359 PubMed
Visel A*, Taher L, Girgis H, May D, Golonzhka O, Hoch R, McKinsey GL, Pattabiraman K, Silberberg SN, Blow MJ, Hansen DV, Nord AS, Akiyama JA, Holt A, Hosseini R, Phouanenavong S, Plajzer-Frick I, Shoukry M, Afzal V, Kaplan T, Kriegstein AR, Rubin EM, Ovcharenko I, Pennacchio LA, Rubenstein JL. A High-Resolution Enhancer Atlas of the Developing Telencephalon. Cell 2013, 152:895-908 PubMed PMC Full Text PMC Free PDF
McKinsey GL, Lindtner S, Trzcinski B, Visel A, Pennacchio LA, Huylebroeck D, Higashi Y, Rubenstein JL. Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch between Cortical and Striatal Interneurons. Neuron 2013, 77:83-98. PubMed
Ariza-Cosano A, Visel A, Pennacchio LA, Fraser HB, Gómez-Skarmeta JL, Irimia M, Bessa J. Differences in enhancer activity in mouse and zebrafish reporter assays are often associated with changes in gene expression. BMC Genomics 2012, 13:713. PubMed Open Access Full Text Open Access PDF
ENCODE Project Consortium (400+ authors incl. Visel A). An integrated encyclopedia of DNA elements in the human genome. Nature 2012, 489:57-74. PubMed Open Access Full Text Open Access PDF
May D, Blow MJ, Kaplan T, McCulley DJ, Jensen BC, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Afzal V, Simpson PC, Rubin EM, Black BL, Bristow J, Pennacchio LA*, Visel A*. Large-scale discovery of enhancers from human heart tissue. Nature Genet 2011, 44:89-93. PubMed PMC Full Text PMC Free PDF
Hochheiser H, Aronow BJ, Artinger K, Beaty TH, Brinkley JF, Chai Y, Clouthier D, Cunningham ML, Dixon M, Donahue LR, Fraser SE, Hallgrimsson B, Iwata J, Klein O, Marazita ML, Murray JC, Murray S, de Villena FP, Postlethwait J, Potter S, Shapiro L, Spritz R, Visel A, Weinberg SM, Trainor PA. The FaceBase Consortium: a comprehensive program to facilitate craniofacial research. Dev Biol 2011, 355:175-82. PubMed
Hess M, Sczyrba A, Egan R, Kim TW, Chokhawala H, Schroth G, Luo S, Clark DS, Chen F, Zhang T, Mackie RI, Pennacchio LA, Tringe SG, Visel A, Woyke T, Wang Z, Rubin EM. (17 authors). Metagenomic discovery of biomass-degrading genes and genomes from cow rumen. Science 2011, 331:463-7. PubMed
Fort A, Fish RJ, Attanasio C, Dosch R, Visel A, Neerman-Arbez M. A liver enhancer in the fibrinogen gene cluster. Blood 2011, 117:276-82. PubMed
Blow MJ, McCulley DJ, Li Z, Zhang T, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Chen F, Afzal V, Bristow J, Ren B, Black BL, Rubin EM, Visel A*, Pennacchio LA*. ChIP-seq Identification of Weakly Conserved Heart Enhancers. Nature Genet 2010. PubMed News and Views PMC Full Text PMC Free PDF
Visel A, Rubin EM, Pennacchio LA. Limits of sequence and functional conservation (News and Views). Nature Genet 2010, 42:557-558. PubMed
Gotea V, Visel A, Westlund JM, Nobrega MA, Pennacchio LA, Ovcharenko I. Homotypic clusters of transcription factor binding sites are a key component of human promoters and enhancers. Genome Res 2010, 20:565-577. PubMed Full Text PDF
Visel A, Zhu Y, May D, Afzal V, Gong E, Attanasio C, Blow MJ, Cohen JC, Rubin EM, Pennacchio LA. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature 2010, 464:409-412. PubMed PMC Full Text PMC Free PDF
Visel A, Rubin EM, Pennacchio LA. Genomic views of distant-acting enhancers. Nature 2009, 461:199-205. PubMed PMC Full Text PMC Free PDF
Visel A*, Blow MJ*, Li Z, Zhang T, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Chen F, Afzal V, Ren B, Rubin EM, Pennacchio LA. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 2009, 457:854-858. PubMed PMC Full Text PMC Free PDF Data Sets
Visel A, Akiyama JA, Shoukry M, Afzal V, Rubin EM, Pennacchio LA. Functional autonomy of distant-acting human enhancers. Genomics 2009, 93:509-13. PubMed PMC Full Text PMC Free PDF
Avraham O, Hadas Y, Vald L, Zisman S, Schejter A, Visel A, Klar A. Transcriptional control of axonal guidance and sorting in dorsal interneurons by the Lim-HD proteins Lhx9 and Lhx1. Neural Dev 2009, 4:21. PubMed Full Text PDF
Visel A, Prabhakar S, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Afzal V, Rubin EM, Pennacchio LA. Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nature Genet 2008, 40:158-60. PubMed PMC Full Text PMC Free PDF Data Sets
Prabhakar S, Visel A, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Morrison H, Fitzpatrick DR, Afzal V, Pennacchio LA, Rubin EM, Noonan JP. Human-specific gain of function in a developmental enhancer. Science 2008, 312:1346-50. PubMed PMC Full Text PMC Free PDF
Rahimov F, Marazita ML, Visel A, ..., Murray JC (23 authors). Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nature Genet 2008, 40:1341-7. PubMed PMC Full Text PMC Free PDF
De Val S, Chi NC, Meadows SM, Minovitsky S, Anderson JP, Harris IS, Ehlers ML, Agarwal P, Visel A, Xu SM, Pennacchio LA, Dubchak I, Krieg PA, Stainier DY, Black BL. Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors. Cell 2008, 135:1053-64. PubMed PMC Full Text PMC Free PDF
Moldrich RX, Laine J, Visel A, Beart PM, Laffaire J, Rossier J, Potier MC. Tmem50b (C21orf4), a candidate for Down syndrome neurophenotypes, encodes an intracellular membrane protein expressed in the rodent brain. Neuroscience 2008, 154(4):1255-1266. PubMed
Visel A, Carson J, Oldekamp J, Warnecke M, Jakubcakova V, Zhou X, Shaw CA, Alvarez-Bolado G, Eichele G. Regulatory Pathway Analysis by High-Throughput In Situ Hybridization. PLoS Genet 2007, 3(10):e234. PubMed Full Text Small PDF Large PDF
Ahituv N, Zhu Y, Visel A, Holt A, Afzal V, Pennacchio LA, Rubin EM. Deletion of ultraconserved elements yields viable mice. PLoS Biol 2007, 5(9):e234. PubMed Full Text Small PDF Large PDF
Visel A, Bristow J, Pennacchio LA. Enhancer identification through comparative genomics. Semin Cell Dev Biol 2007, 18(1):140-52. PubMed PMC Full Text PMC Free PDF
Lein ES, Hawrylycz MJ, ..., Visel A, ..., Jones AR (108 authors). Genome-wide atlas of gene expression in the adult mouse brain. Nature 2007, 445(7124):168-76. PubMed
Visel A, Minovitsky S, Dubchak I, Pennacchio LA. VISTA Enhancer Browser--a database of tissue-specific human enhancers. Nucleic Acids Res 2007, 35:D88-92. PubMed Full Text Small PDF Large PDF
Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM. In vivo enhancer analysis of human conserved non-coding sequences. Nature 2006, 444(7118):499-502. PubMed
Visel A, Alvarez-Bolado G, Thaller C, Eichele G. Comprehensive analysis of the expression patterns of the adenylate cyclase gene family in the developing and adult mouse brain. J Comp Neurol 2006, 496(5):684-97. PubMed
Yaylaoglu MB, Titmus A, Visel A, Alvarez-Bolado G, Thaller C, Eichele G. Comprehensive expression atlas of fibroblast growth factors and their receptors generated by a novel robotic in situ hybridization platform. Dev Dyn 2005, 234(2):371-86. PubMed Full Text PDF
Schumacher S, Laass K, Kant S, Shi Y, Visel A, Gruber AD, Kotlyarov A, Gaestel M. Scaffolding by ERK3 regulates MK5 in development. EMBO J 2004, 23(24):4770-9. PubMed Full Text PDF
Plas DT, Visel A, Gonzalez E, She WC, Crair MC. Adenylate Cyclase 1 dependent refinement of retinotopic maps in the mouse. Vision Res 2004, 44(28):3357-64. PubMed
Danilova N, Visel A, Willett CE, Steiner LA. Expression of the winged helix/forkhead gene, foxn4, during zebrafish development. Dev Brain Res 2004, 153(1):115-9. PubMed
Visel A, Thaller C, Eichele G. GenePaint.org: an atlas of gene expression patterns in the mouse embryo. Nucleic Acids Res 2004, 32:D552-6. PubMed Full Text PDF
Herzig U, Cadenas C, Sieckmann F, Sierralta W, Thaller C, Visel A, Eichele G. Development of high-throughput tools to unravel the complexity of gene expression patterns in the mammalian brain. Novartis Found Symp 2001, 239:129-46. PubMed

last edited Dec 2013