Project description:Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we show that Dcaf11 (Ddb1- and Cul4-associated factor 11) participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs). The deletion of Dcaf11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is also greatly compromised. Mechanistically, Dcaf11 targets Kap1 (KRAB-associated protein 1) for ubiquitination-mediated degradation, leading to the activation of Zscan4 downstream enhancer and the removal of heterochromatic H3K9me3 at telomere/subtelomere regions. Our study therefore demonstrates that Dcaf11 plays important roles in telomere elongation in early embryos and ESCs through activating Zscan4.
Project description:Our study demonstrates that Dcaf11 plays important roles in telomere elongation in early embryos and ESCs through activating Zscan4.
Project description:Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis through the so-called alternative lengthening of telomere (ALT) mechanism. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we showed that Dcaf11 participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs) in a telomerase-independent manner. The deletion of Dcaf11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is greatly compromised. Mechanistically, DCAF11 reactivates Zscan4 and facilitates the removal of heterochromatic H3K9me3 at telomere/subtelomere regions through targeting TRIM28 for ubiquitination-mediated degradation. Our study therefore demonstrates that the ALT factor Dcaf11 plays important roles in telomere elongation in early embryos and ESCs.
Project description:Trophoblast lineages, as the precursor of placenta, are essential for post-implantation embryo survival. However, the regulatory networks for trophoblast development remains incompletely understood. Here, we identified CITED1 as a regulator to induce trophoblast-like differentiation from mESCs. Overexpression of CITED1 in ESCs prompted differentiation towards trophoblast accompanying with elevated expression of trophoblast marker genes. To evaluate the ability of CITED1 to induce trophoblast differentiation at a genome-wide scale, we compared the global transcriptional profiles between CITED1 overexpressing cells and control ESCs by Affymetrix microarray analysis at day 1 and day 2 after transfection. We used microarrays to identify genes affected by CITED1 overexpression in mouse ESCs.
Project description:Analysis of mouse ESCs overexpressing HDAC6. Histone deacetylase 6 (Hdac6) was discovered as a deacetylase of α-tubulin and functions in cell migration, immunity and resistance to virus infection in vitro. HDAC6 overexpression ESCs and control ESCs were selected for RNA extraction and hybridization on Agilent microarrays. Results provide insight into the role of HDAC6 in the mouse ESCs.
Project description:MeGRX232 and MeGRX360 are drought-inducible CC-type glutaredoxins in cassava. Overexpression of them in Arabidopsis caused different effects on plant growth. We used microarray to identified the different expression genes in MeGRX232-OE and MeGRX360-OE Arabidopsis