Welcome to Yue's home

PhD research : Chromatin-remodeling multiprotein complexes are critically involved in processes that include transcription, replication, chromatin assembly, and chromosome condensation. Furthermore, multiple human diseases, including Alzheimer's disease and several types of cancer, are caused by mutations in chromatin-remodeling complexes. One of these complexes is the NuRD complex (nucleosome remodelling and histone deacetylase).In the regulation or modulation of many cellular and developmental processes, the multiprotein Mi-2/NuRDcomplex was first proposed through histone deacetylation to repress gene repression, but the recent study of Mi-2/NuRD complex was shown to be involved in gene expression activation as well. Thus, the biological functions of Mi-2/NuRD complex can be fully understood only when the consequences of its association in biochemical niche are defined. The C. elegans genome encodes orthologues of all components of the vertebrate Mi-2/NuRD complex, among them the two Mi-2 homologues LET-418 and CHD-3. LET-418 and CHD-3 were shown to play essential and partially redundant roles during development. With both candidate approach and systematic screen, we have applied genetic and biochemical techniques to elucidate the functions of LET-418, including the development of a chromatin immuno-precipitation protocol and SSH (suppression subtractive hybridization) and RNA interference screens to assay its targets and characterize their functions. Interestingly, though no successful hit by using conventional forward suppressor screen, we identified two suppressors of the lethality of let-418 mutants by performed RNAi screen on the up ¨Cregulated downstream target genes from SSH library (**See also Ariana Kaeser,s thesis in detail as this SSH library has been divided in half ) and this proves the high quality of our SSH library. We also show LET-418 together with LIN-1/ETS directly binds promoter of the lin-39 /Hox gene to repress its expression and LET-418 directly regulates Lag-2 in Lin-12/Notch pathway. To further understand the roles of LET-418 in other pathways, we have performed a SSH screen to identify some novel targets of LET-418. We confirmed that the gene Clp1 ChIP F59A2.4 (clp-1) is over-expressed in dysfunctional LET-418 animals that is involved in 3¡¯end formation and polyadenylation transcriptional machinery. The confirmed dis-regulations of sqt-2 and sqt-3 make a putative link between LET-418/Mi-2 and TGF beta pathway. Furthermore, we identified two suppressors of the lethality of let-418 mutants by performed RNAi screen on the up ¨Cregulated downstream target genes from SSH library and proved the good quality of our SSH library. Unexpectedly, the dysfunctional CHD-3 animals shows a heat shock lethal phenotype but its mechanism remains unclear. We also found that dysfunctional LET-418 and other NuRD component animals have partially relaxed requirement of RNA dependent RNA polymerase RRF-1 during RNAi and it suggests that LET-418 and NuRD could play somehow roles in RNAi pathway NuRDin RNAi Aka : I'm particularly interested in involvements of two C.elegans homologues of human dermatomyositis -specific autoantigen Mi-2/NuRD(Nucleosome Remodeling and histone Deacetylation) complex in different pathways.The two proteins, LET-418 and CHD-3, possess shared and unique functions and are essential for development of C. elegans. Particularly, we found that the two proteins play an important role for RTK/Ras and Notch signalling, two pathways that are implicated in cancer and Alzheimer's disease in humans. Genetic and biochemical data suggest that LET-418 and CHD-3 may act as components of different C. elegans NuRD complexes (CeNuRD) . I am currently developing the worm-specific technical ?platform? for screening and confirming / characterizing some of the global developmental stage?specific / tissue?specific in/ direct target genes of C.elegans Mi-2 / NuRD complex, which combines the chromatin immunoprecipitation protocol , +/- chipL/SSHPCR, single worm quantitative RT-PCR, Rapid one-step and enhanced RNAi protocol using my latest developed RNA i pYZ-vector series , probably mass spectrometry, and so on. Latest publications: Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F. 2003 Genetics: influence of TOR kinase on lifespan in C. elegans. Nature. 426(6967):620. Guerry F*, Marti CO* zhang Y*, Moroni PS, Jaquiery E, Muller F(2007). (* co¨Cfirst author) The Mi-2 nucleosome-remodeling protein LET-418 is targeted via LIN-1/ETS to the promoter of lin-39/Hox during vulval development in C. elegans. Dev Biol. 2007 Jun 15; 306(2):469-79.Epub 2007 Mar 24. Takacs-Vellai K, Vellai T, Chen EB, Zhang Y, Guerry F, Stern MJ, Muller F(2006) Transcriptional control of Notch signaling by a HOX and a PBX/EXD protein during vulval development in C. elegans. Dev Biol. 2007 Feb 15;302(2):661-9. Epub 2006 Oct 4.

Current work: . Adapted C.elegans toolkit on mammalian cell line to make human HSF1 knock-in stable cell line carrying out systematic study of ChIP-chip, TAP purification etc. .. Candidate approach study of crosstalk of HIF1, PKA, HSF1 and p53 in breast cancer. ... Invited by >Transgenic Research > as peer reviewer to review manuscript . Invited by >Genetics and Epigenetics > as peer reviewer to review manuscripts .