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Expression data from Ankrd11Yod/+ and WT embryonic cortical neurospheres

ABSTRACT: Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin, colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial epigenetic regulator of neural development that controls histone acetylation and gene expression, thereby providing a likely explanation for its association with cognitive dysfunction and ASD. We used microarrays to compare the gene expression profile in embryonic neurospheres prepared from neocortices of WT and Ankrd11Yod/+ mice

ORGANISM(S): Mus musculus

PROVIDER: GSE63303 | GEO | 2014/11/15

SECONDARY ACCESSION(S): PRJNA267240

REPOSITORIES: GEO

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Expression data from Ankrd11Yod/+ and WT embryonic cortical neurospheres

Project description:Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin, colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial epigenetic regulator of neural development that controls histone acetylation and gene expression, thereby providing a likely explanation for its association with cognitive dysfunction and ASD. We used microarrays to compare the gene expression profile in embryonic neurospheres prepared from neocortices of WT and Ankrd11Yod/+ mice E14.5 cortical secondary neurosheres 5 days post-passage were collected and total RNA extracted. cDNA was hybridized on Affymetrix Mouse Gene 2.0 ST Array and gene expression was analyzed using Parterk software. In total, 6 Ankrd11Yod/+ and 5 WT embryos were used.

2014-11-15 | E-GEOD-63303 | biostudies-arrayexpress

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Project description:Previous study demonstrated that HDAC3 has a critical role in MM proliferation; however, the underlying mechanism has not yet been elucidated. We identify that HDAC3 inhibition targets DNMT1 through dual regulations. We demonstrate that knockdown of DNMT1 leads to apoptosis and significant growth inhibition in myeloma cells. HDAC3 inhibition by gene silencing or HDAC3 selective inhibitor BG45 downregulates an oncoprotein c-Myc through its acetylation. c-Myc directly regulates DNMT1 expression at its enhancer region. Furthermore, HDAC3 directly regulates the stability of DNMT1 protein through its acetylation. Pharmaceutical inhibition of HDAC3 and DNMT1 synergistically induce MM growth inhibition in in vitro and in vivo settings. The goal of this analysis is to identify genes whose expression changes after shRNA-mediated knockdown of HDAC3 or DNMT1 using the human U133 plus 2.0 Affymetrix GeneChip in myeloma cell line (MM.1S).

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