Project description:We evaluated differentially expressed genes (DEGs) between hepatocellular carcinoma cell lines (Hep3B, SNU449, and PLC/PRF/5) treated with ATAD2 siRNA or control using Affymetrix array data whether ATAD2 could be potential target in hepatocellular carcinoma.
Project description:ATAD2, expressed predominantly in embryonic stem cells as well as in spermatogenic cells emerges as a pivotal regulator of chromatin dynamics by mediating chromatin-bound histone chaperone turnover. Here, investigating the role of ATAD2 in spermatogenesis, we show that through its preponderant expression in haploid male germ cells, ATAD2 modulates the HIRA-dependent H3.3 genome localization and H3.3-dependent gene transcriptional regulation. Furthermore, by influencing histone eviction and the assembly of protamines, it ensures proper chromatin condensation and genome packaging in mature spermatozoa. The disruption of Atad2 results in aberrant mature spermatozoa genome organization, impacting male fertility. Collectively, these findings confirm the occurrence of an overlooked chromatin dynamic regulatory level controlling histone deposition-removal balance, depending on an ATAD2-controlled histone chaperone-chromatin interaction.
Project description:ATAD2, expressed predominantly in embryonic stem cells as well as in spermatogenic cells emerges as a pivotal regulator of chromatin dynamics by mediating chromatin-bound histone chaperone turnover. Here, investigating the role of ATAD2 in spermatogenesis, we show that through its preponderant expression in haploid male germ cells, ATAD2 modulates the HIRA-dependent H3.3 genome localization and H3.3-dependent gene transcriptional regulation. Furthermore, by influencing histone eviction and the assembly of protamines, it ensures proper chromatin condensation and genome packaging in mature spermatozoa. The disruption of Atad2 results in aberrant mature spermatozoa genome organization, impacting male fertility. Collectively, these findings confirm the occurrence of an overlooked chromatin dynamic regulatory level controlling histone deposition-removal balance, depending on an ATAD2-controlled histone chaperone-chromatin interaction.
Project description:ATPase Family AAA domain containing 2 (ATAD2) expression is elevated in many cancer types including ovarian cancer. Therefore, we analyzed the role of ATAD2 in ovarian cancer. Pharmacological inhibition of ATAD2 expression in ovarian cancer cell lines resulted in decreased proliferation, and increased cell death.
Project description:MYTHO protein is a recently described novel regulator of autophagy and mass in skeletal muscles. Using immunoprecipitation assay, we found that the nuclear protein ATAD2 (ATPase family AAA domain containing 2) interacts with MYTHO protein in C2C12 myoblasts. The functional role of ATAD2 in skeletal muscle cells was assessed by using transient and stable Atad2 knockdown (KD) in C2C12 myoblasts. Atad2 KD significantly increased myoblast proliferation rate, S-phase entry, overall cell viability, and early differentiation into myotubes. However, Atad2 KD also elicited myotube atrophy and accumulation of autophagy-related proteins due to inhibition of autophagosome fusion with lysosomes and/or lysosome dysfunction. LAMP1 staining confirmed the presence of enlarged lysosomes in Atad2 KD cells. Additionally, genes involved in lysosome function and integrity including Rab7, Rab29, Nrbf2, and Cathepsin L were downregulated in Atad2 KD cells. Collectively, these results indicate that ATAD2 is a critical regulator of muscle cell proliferation, differentiation, and autophagy.
Project description:Although the conserved AAA ATPase â bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2âs function as a facilitator of general chromatin-templated activities such as transcription. Transcriptomic analyses comparing ES cells stably expressing anti-Atad2 shRNA versus cells expressing control shRNA, in day 3 LIF (-) differentiating ES cells (3 replicates for each condition) were performed using the Illumina MouseWG-6 v2.0 expression beadchip technology
Project description:Although the conserved AAA ATPase – bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2’s function as a facilitator of general chromatin-templated activities such as transcription.
Project description:Although the conserved AAA ATPase – bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2’s function as a facilitator of general chromatin-templated activities such as transcription.
Project description:Although the conserved AAA ATPase – bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2’s function as a facilitator of general chromatin-templated activities such as transcription.