Project description:Multicellular organisms develop new structures by initiating specific gene regulatory programs through coordinated changes at the transcriptional and chromatin levels. Master transcription factors orchestrate such global changes but the underlying molecular mechanisms remain unclear. Here we focus on LEAFY (LFY), a key regulator of flower development in angiosperms. The resolution of the crystallographic structure of its N-terminal domain shows that it forms an unanticipated Sterile Alpha Motif (SAM) domain. This domain drives LFY oligomerization, which we establish to be essential for LFY floral switch function. Combining in vitro and in vivo experiments, we demonstrate that oligomerization facilitates LFY binding to DNA regions with multiple binding sites. Moreover, genome-wide analyses reveal an additional prominent role for the oligomerization domain: it confers upon LFY the capacity to bind to closed chromatin regions. This novel property, combined with its previously demonstrated capacity to recruit chromatin remodelers, indicates that LFY controls floral fate by acting as a plant pioneer transcription factor.
Project description:Nucleotide-binding oligomerization domain 2 (Nod2) signaling is critical for human health.To figure out the clinical relevance of NOD2 ligands, the investigators plan to evaluate the change of NOD2 ligands in inflammatory bowel diseases (IBD), CRC, atherosclerotic cardiovascular disease (ACVD), and type 2 diabetes mellitus (DM2 ).
Project description:<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate (EEC) syndrome. Underlying molecular mechanism of these mutations however remain unclear. Here we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and by unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify an unreported disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>
Project description:We investigated the transcriptional effects of p63 binding by analyzing ME180 cells depleted for all p63 isoforms via expression of a small hairpin RNA (shRNA) targeting the p63 oligomerization domain. Keywords: differential expression profiling from transcription factor depletion
Project description:FUSCA3 (FUS3) is a B3 domain transcription factor that is a member of the LEAFY COTYLEDON (LEC) group of genes. The LEC genes encode proteins that also include LEC2, a B3 domain factor related to FUS3, and LEC1, a CCAAT box binding factor. LEC1, LEC2 and FUS3 are essential for plant embryo development. We report ChIP-chip experiments using the Affymetrix tiling array to globally map binding sites for FUS3. Fangfang Wang and Sharyn E. Perry (2013) Plant Physiology preview
Project description:We determine the genome-wide transcriptome, enhancer landscape and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer. Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration.
Project description:This study identified LEAFY (LFY) as a pioneer transcription factor. We made use of 35S:LFY-GR, an inducible version of the LFY protein fused to the rat glucocorticoid hormone binding domain. In root explants, steroid activated LFY-GR triggers synchronous and abundant flower induction (PMID: 15225291). We combined LFY ChIP-seq, MNase-seq before and after LFY binding and time-course RNA-seq in 35S:LFY-GR root explants to characterize the role of LFY as a pioneer transcription factor.