Cited by 167Developmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanismsGenomics and Chromatin Dynamics

Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis

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Mandel, Shmuel, Rechavi, Gideon, Gozes, Illana·2007·Developmental Biology

Abstract

Complete deficiency in activity-dependent neuroprotective protein (ADNP) results in neural tube closure defects and death at days 8.5-9.5 of gestation in the mouse (E8.5-9.5). To elucidate ADNP associated pathways, Affymetrix 22,690-oligonucleotide-based microarrays were used on ADNP knockout and control mouse embryos (E9) separated completely from extra embryonic tissue. Marked differences in expression profiles between ADNP-deficient embryos and ADNP-expressing embryos were discovered. Specifically, a group of dramatically up-regulated gene transcripts in the ADNP-deficient embryos were clustered into a family encoding for proteins enriched in the visceral endoderm such as apolipoproteins, cathepsins and methallotionins. In contrast, a down regulated gene cluster associated with ADNP-deficiency in the developing embryo consisted of organogenesis markers including neurogenesis (Ngfr, neurogenin1, neurod1) and heart development (Myl2). The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. A comparison between non-differentiated and neuro-differentiated P19 cells revealed increased chromatin interaction of ADNP with chromatin from differentiated cells. These results place ADNP at a crucial point of gene regulation, repressing potential endoderm genes and enhancing genes associated with organogenesis/neurogenesis.

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Crossref · 10.1016/j.ydbio.2006.11.039

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  • Among genes reported as differentially expressed in Adnp-/- and Adnp+/- mice, only PLAGL2 was differentially regulated in the patients.

    “Of the other genes reported as differentially expressed in Adnp-/-23 and Adnp+/-18 mice (down: CCNC, TMPO, PLAGL2; up: ABCF3), only PLAGL2 was found to be differentially regulated in our patients (Supplementary Fig. 3e).”

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Authors
Mandel, S., Rechavi, G., & Gozes, I.
Affiliations
Tel Aviv University (IL)
Corresponding author
Gozes, Illana
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2007-03
Volume
303
Issue
2
Pages
814-824
ISSN
0012-1606 (ISSN-L)
OpenAlex
W2124865989
Cited by
167
References
47
Citations by year
2026: 8 · 2025: 11 · 2024: 14 · 2023: 11 · 2022: 10 · 2021: 3 · 2020: 12 · 2019: 10 · 2018: 11 · 2017: 12 · 2016: 9 · 2015: 9 · 2014: 11 · 2013: 4 · 2012: 6
FWCI
2.18
Type
journal article
Language
en
Open access
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Israel Science Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
ADNP, chromatin binding, gene expression regulation, organogenesis, neurogenesis, heart development, promoter binding, P19 cells, gene expression profiling
MeSH terms
Chromobox Protein Homolog 5, Animals, Base Sequence, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Female, Models, Biological, Nerve Tissue Proteins, Pregnancy, DNA Primers, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Gene Expression Profiling, Embryonic Development, Mice

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