Novel Evolutionary-conserved Role for the Activity-dependent Neuroprotective Protein (ADNP) Family That Is Important for Erythropoiesis
Open accessAbstract
BACKGROUND: ADNP is vital for embryonic development. Is this function conserved for the homologous protein ADNP2? RESULTS: Down-regulation/silencing of ADNP or ADNP2 in zebrafish embryos or mouse erythroleukemia cells inhibited erythroid maturation, with ADNP directly associating with the β-globin locus control region. CONCLUSION: ADNPs are novel molecular regulators of erythropoiesis. SIGNIFICANCE: New regulators of globin synthesis are suggested. Activity-dependent neuroprotective protein (ADNP) and its homologue ADNP2 belong to a homeodomain, the zinc finger-containing protein family. ADNP is essential for mouse embryonic brain formation. ADNP2 is associated with cell survival, but its role in embryogenesis has not been evaluated. Here, we describe the use of the zebrafish model to elucidate the developmental roles of ADNP and ADNP2. Although we expected brain defects, we were astonished to discover that the knockdown zebrafish embryos were actually lacking blood and suffered from defective hemoglobin production. Evolutionary conservation was established using mouse erythroleukemia (MEL) cells, a well studied erythropoiesis model, in which silencing of ADNP or ADNP2 produced similar results as in zebrafish. Exogenous RNA encoding ADNP/ADNP2 rescued the MEL cell undifferentiated state, demonstrating phenotype specificity. Brg1, an ADNP-interacting chromatin-remodeling protein involved in erythropoiesis through regulation of the globin locus, was shown here to interact also with ADNP2. Furthermore, chromatin immunoprecipitation revealed recruitment of ADNP, similar to Brg1, to the mouse β-globin locus control region in MEL cells. This recruitment was apparently diminished upon dimethyl sulfoxide (DMSO)-induced erythrocyte differentiation compared with the nondifferentiated state. Importantly, exogenous RNA encoding ADNP/ADNP2 significantly increased β-globin expression in MEL cells in the absence of any other differentiation factors. Taken together, our results reveal an ancestral role for the ADNP protein family in maturation and differentiation of the erythroid lineage, associated with direct regulation of β-globin expression.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The most prominent phenotype of ADNP knockdown in zebrafish is defective erythropoiesis.
“the most prominent phenotype of ADNP knockdown in zebrafish is defective erythropoiesis (63).”
From Genetics and genomics of autism spectrum disorder: embracing complexity (2015) · cites this paper as [63]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stages of embryonic development of the zebrafish
Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B., & Schilling, T. F. (1995) · Developmental Dynamics · doi:10.1002/aja.1002030302 · Cited by 12,037 · see citing works
Kozak, M. (1986) · Cell · doi:10.1016/0092-8674(86)90762-2 · Cited by 4,741 · see citing works
Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
Fong, G.-H., Rossant, J., Gertsenstein, M., & Breitman, M. L. (1995) · Nature · doi:10.1038/376066a0 · Cited by 2,606 · see citing works
Effective targeted gene ‘knockdown’ in zebrafish
Nasevicius, A., & Ekker, S. C. (2000) · Nature Genetics · doi:10.1038/79951 · Cited by 2,485 · see citing works
Zebrafish hox Clusters and Vertebrate Genome Evolution
Amores, A., Force, A. G., Yan, Y., Joly, L., Amemiya, C. T., Fritz, A., Ho, R. K., Langeland, J. A., Prince, V., Wang, Y.-L., et al. (1998) · Science · doi:10.1126/science.282.5394.1711 · Cited by 1,737 · see citing works
Friend, C., Scher, W., Holland, J. G., & Satô, T. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.2.378 · Cited by 1,352 · see citing works
The zebrafish midblastula transition
Kane, D. A., & Kimmel, C. B. (1993) · Development · doi:10.1242/dev.119.2.447 · Cited by 722 · see citing works
Comparative analysis of proteome and transcriptome variation in mouse
Ghazalpour, A., Bennett, B., Petyuk, V. A., Orozco, L., Hagopian, R., Mungrue, I. N., Farber, C. R., Sinsheimer, J., Kang, H. M., Furlotte, N., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001393 · Cited by 624 · see citing works
Yelon, D. L., Horne, S., & Stainier, D. Y. R. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9406 · Cited by 506 · see citing works
The cloche and spadetail Genes Differentially Affect Hematopoiesis and Vasculogenesis
Thompson, M. A., Ransom, D. G., Pratt, S. J. P., MacLennan, H., Kieran, M. W., Detrich, H. W., Vail, B., Huber, T. L., Paw, B. H., Brownlie, A., et al. (1998) · Developmental Biology · doi:10.1006/dbio.1998.8887 · Cited by 495 · see citing works
Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development
Porter, F. D., Drago, J., Xu, Y., Cheema, S. S., Wassif, C. A., Huang, S.-P., Lee, E., Grinberg, A., Massalas, J. S., Bodine, D. M., et al. (1997) · Development · doi:10.1242/dev.124.15.2935 · Cited by 491 · see citing works
Myelopoiesis in the zebrafish, Danio rerio
Bennett, C. M., Kanki, J. P., Rhodes, J., Liu, T. X., Paw, B. H., Kieran, M. W., Langenau, D. M., Delahaye-Brown, A., Zon, L. I., Fleming, M. D., et al. (2001) · Blood · doi:10.1182/blood.v98.3.643 · Cited by 423 · see citing works
The ‘definitive’ (and ‘primitive’) guide to zebrafish hematopoiesis
Davidson, A. J., & Zon, L. I. (2004) · Oncogene · doi:10.1038/sj.onc.1207943 · Cited by 419 · see citing works
Bassan, M., Zamostiano, R., Davidson, A., Pinhasov, A., Giladi, E., Perl, O., Bassan, H., Blat, C., Gibney, G., Glazner, G. W., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721283.x · Cited by 394 · see citing works
Self-citationChromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers
de la Serna, I. L., Ohkawa, Y., & Imbalzano, A. N. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1882 · Cited by 376 · see citing works
Death before birth: clues from gene knockouts and mutations
Copp, A. J. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89008-3 · Cited by 368 · see citing works
Transcriptional Specificity of Human SWI/SNF BRG1 and BRM Chromatin Remodeling Complexes
Kadam, S., & Emerson, B. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00034-0 · Cited by 340 · see citing works
Pelster, B., & Burggren, W. W. (1996) · Circulation Research · doi:10.1161/01.res.79.2.358 · Cited by 293 · see citing works
Reverse transcriptase template switching and false alternative transcripts
Cocquet, J., Chong, A., Zhang, G., & Veitia, R. A. (2006) · Genomics · doi:10.1016/j.ygeno.2005.12.013 · Cited by 269 · see citing works
Cloning and Characterization of the Human Activity-dependent Neuroprotective Protein
Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007416200 · Cited by 251 · see citing works
Self-citationPositional cloning of the zebrafish sauternes gene: a model for congenital sideroblastic anaemia
Brownlie, A., Donovan, A., Pratt, S. J. P., Paw, B. H., Oates, A. C., Brugnara, C., Witkowska, H. E., Sassa, S., & Zon, L. I. (1998) · Nature Genetics · doi:10.1038/3049 · Cited by 244 · see citing works
Activity-dependent neuroprotective protein: a novel gene essential for brain formation
Pinhasov, A., Mandel, S., Torchinsky, A., Giladi, E., Pittel, Z., Goldsweig, A. M., Servoss, S. J., Brenneman, D. E., & Gozes, I. (2003) · Developmental Brain Research · doi:10.1016/s0165-3806(03)00162-7 · Cited by 239 · see citing works
Self-citationVulih-Shultzman, I., Pinhasov, A., Mandel, S., Grigoriadis, N., Touloumi, O., Pittel, Z., & Gozes, I. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.129551 · Cited by 219 · see citing works
Self-citationBrand, M., Ranish, J. A., Kummer, N. T., Hamilton, J., Igarashi, K., Francastel, C., Chi, T. H., Crabtree, G. R., Aebersold, R. H., & Groudine, M. T. (2003) · Nature Structural & Molecular Biology · doi:10.1038/nsmb713 · Cited by 210 · see citing works
3 Ontogeny of hematopoiesis: Examining the emergence of hematopoietic cells in the vertebrate embryo
Galloway, J. L., & Zon, L. I. (2003) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(03)53004-6 · Cited by 186 · see citing works
SCL and associated proteins distinguish active from repressive GATA transcription factor complexes
Tripic, T., Deng, W., Cheng, Y., Zhang, Y., Vakoc, C. R., Gregory, G. D., Hardison, R. C., & Blobel, G. A. (2008) · Blood · doi:10.1182/blood-2008-07-169417 · Cited by 176 · see citing works
Characterization of embryonic globin genes of the zebrafish
Brownlie, A., Hersey, C., Oates, A. C., Paw, B. H., Falick, A. M., Witkowska, H. E., Jonathan Flint, C., Higgs, D. R., Jessen, J. R., Bahary, N., et al. (2003) · Developmental Biology · doi:10.1016/s0012-1606(02)00041-6 · Cited by 168 · see citing works
Mandel, S., Rechavi, G., & Gozes, I. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2006.11.039 · Cited by 167 · see citing works
Self-citationBultman, S. J., Gebuhr, T. C., & Magnuson, T. (2005) · Genes & Development · doi:10.1101/gad.1364105 · Cited by 155 · see citing works
Mandel, S., & Gozes, I. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704756200 · Cited by 150 · see citing works
Self-citationWoods, B. T. (2009) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199542758.001.0001 · Cited by 150 · see citing works
Ziv, L., Levkovitz, S., Toyama, R., et al. (2005) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2005.01315.x · Cited by 135 · see citing works
Ikaros expression as a marker for lymphoid progenitors during zebrafish development
Willett, C., Kawasaki, H., Amemiya, C. T., Lin, S., & Steiner, L. A. (2001) · Developmental Dynamics · doi:10.1002/dvdy.1223 · Cited by 125 · see citing works
BRG1 requirement for long-range interaction of a locus control region with a downstream promoter
Kim, S., Bultman, S. J., Kiefer, C. M., Dean, A., & Bresnick, E. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806420106 · Cited by 125 · see citing works
Griffin, C. T., Brennan, J. A., & Magnuson, T. (2007) · Development · doi:10.1242/dev.010090 · Cited by 121 · see citing works
Chapter 1 Ontogeny of Erythropoiesis in the Mammalian Embryo
McGrath, K. E., & Palis, J. (2008) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(07)00001-4 · Cited by 110 · see citing works
Itoh, M., Kudoh, T., Dedekian, M., Kim, C., & Chitnis, A. B. (2002) · Development · doi:10.1242/dev.129.10.2317 · Cited by 101 · see citing works
Basu, P., Morris, P. E., Haar, J. L., Wani, M. A., Lingrel, J. B., Gaensler, K. M. L., & Lloyd, J. A. (2005) · Blood · doi:10.1182/blood-2005-02-0674 · Cited by 99 · see citing works
Iuchi, I., & Yamamoto, M. (1983) · Journal of Experimental Zoology · doi:10.1002/jez.1402260311 · Cited by 92 · see citing works
Mandel, S., Spivak-Pohis, I., & Gozes, I. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-9013-y · Cited by 91 · see citing works
Self-citationPalevitch, O., Kight, K. E., Abraham, E., Wray, S., Zohar, Y., & Gothilf, Y. (2006) · Cell and Tissue Research · doi:10.1007/s00441-006-0279-0 · Cited by 87 · see citing works
Self-citationMcArthur, M., Gerum, S. E., & Stamatoyannopoulos, G. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4969 · Cited by 85 · see citing works
Dresner, E., Agam, G., & Gozes, I. (2010) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2010.06.004 · Cited by 65 · see citing works
Self-citationNon-cell autonomous requirement for thebloodlessgene in primitive hematopoiesis of zebrafish
Liao, E. C.-W., Trede, N. S., Ransom, D. G., Zapata, A. G., Kieran, M. W., & Zon, L. I. (2002) · Development · doi:10.1242/dev.129.3.649 · Cited by 62 · see citing works
Uoshima, N., Ozawa, M., Kimura, S. H., et al. (1995) · British Journal of Haematology · doi:10.1111/j.1365-2141.1995.tb05240.x · Cited by 48 · see citing works
Recombinant activity-dependent neuroprotective protein protects cells against oxidative stress
Steingart, R. A., & Gozes, I. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.03.029 · Cited by 48 · see citing works
Self-citationHattangadi, S. M., Burke, K. A., & Lodish, H. F. (2010) · Blood · doi:10.1182/blood-2009-07-235093 · Cited by 48 · see citing works
Differential Regulation of Primitive Myelopoiesis in the Zebrafish by Spi-1/Pu.1 and C/ebp1
Su, F., Juarez, M. A., Cooke, C. L., LaPointe, L. D., Shavit, J. A., Yamaoka, J. S., & Lyons, S. E. (2007) · Zebrafish · doi:10.1089/zeb.2007.0505 · Cited by 46 · see citing works
Xu, Z., Meng, X., Cai, Y., Koury, M. J., & Brandt, S. J. (2006) · Biochemical Journal · doi:10.1042/bj20060873 · Cited by 42 · see citing works
Huo, X.-F., Yu, J., Peng, H., et al. (2006) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-006-9229-0 · Cited by 39 · see citing works
Kushnir, M., Dresner, E., Mandel, S., & Gozes, I. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05173.x · Cited by 38 · see citing works
Self-citationBiosynthesis of erythrocyte membrane protein band 3 in DMSO‐induced friend erythroleukemia cells
Sabban, E. L., Sabatini, D. D., Marchesi, V. T., et al. (1980) · Journal of Cellular Physiology · doi:10.1002/jcp.1041040217 · Cited by 38 · see citing works
Distinct Roles for SCL in Erythroid Specification and Maturation in Zebrafish
Juarez, M. A., Su, F., Chun, S., Kiel, M. J., & Lyons, S. E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507998200 · Cited by 25 · see citing works
Li, W., Ralphs, K. L., Slack, J. M. W., & Tosh, D. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.10.017 · Cited by 19 · see citing works
fgf1 is required for normal differentiation of erythrocytes in zebrafish primitive hematopoiesis
Songhet, P., Adzic, D., Reibe, S., et al. (2007) · Developmental Dynamics · doi:10.1002/dvdy.21056 · Cited by 17 · see citing works
Pessano, S., McNab, A. R., & Rovera, G. (1981) · PubMed · Cited by 15 · see citing works
Paw, B. H. (2001) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2000.0354 · Cited by 13 · see citing works
Differentiation of murine erythroleukemic (friend) cells: An in vitro model of erythropoiesis
Orkin, S. H. (1978) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02618181 · Cited by 11 · see citing works
Regulation of differentiation in normal and transformed erythroid cells
Rifkind, R. A., Marks, P. A., Bank, A., et al. (1978) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02618182 · Cited by 7 · see citing works
Dzierzak, E. A. (2013) · Blood · doi:10.1182/blood.v122.21.sci-4.sci-4 · Cited by 6 · see citing works
Precise quantification of haemoglobin in erythroid precursors and plasma
Toobiak, S., Sher, E. A., Shaklai, M., et al. (2011) · International Journal of Laboratory Hematology · doi:10.1111/j.1751-553x.2011.01338.x · Cited by 4 · see citing works
Serum-free media for murine erythroleukemia cells still not as good as serum-supplemented media
Ahearn, G. S., Majumdar, S., & Daehler, C. C. (1992) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02634236 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Malishkevich, A., Amram, N., Hacohen-Kleiman, G., Magen, I., Giladi, E., & Gozes, I. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.138 · Cited by 109 · see citing works
Self-citation
- Authors
- Dresner, E., Malishkevich, A., Arviv, C., Leibman Barak, S., Alon, S., Ofir, R., Gothilf, Y., & Gozes, I.
- Affiliations
- Tel Aviv University (IL)
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Gozes, Illana
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 287
- Issue
- 48
- Pages
- 40173-40185
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3504731
- OpenAlex
- W2080512822
- Cited by
- 47
- References
- 62
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 1
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ADNP, erythropoiesis, erythroid maturation, beta-globin locus control region, beta-globin expression, SMARCA4, chromatin remodeling, erythroleukemia cells, zebrafish embryos, hemoglobin synthesis, gene silencing, erythroid differentiation
- MeSH terms
- Animals, Erythropoiesis, Multigene Family, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Zebrafish, Evolution, Molecular, Zebrafish Proteins, Erythroid Cells, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
