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Full-Text Articles in Life Sciences
Increased Expression Of The Tight Junction Protein Tjp1/Zo-1 Is Associated With Upregulation Of Taz-Tead Activity And An Adult Tissue Stem Cell Signature In Carfilzomib-Resistant Multiple Myeloma Cells And High-Risk Multiple Myeloma Patients, Irene Riz, Robert G. Hawley
Increased Expression Of The Tight Junction Protein Tjp1/Zo-1 Is Associated With Upregulation Of Taz-Tead Activity And An Adult Tissue Stem Cell Signature In Carfilzomib-Resistant Multiple Myeloma Cells And High-Risk Multiple Myeloma Patients, Irene Riz, Robert G. Hawley
Anatomy and Regenerative Biology Faculty Publications
Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomiband carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfzlike phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature. siRNA-mediated knockdown of TJP1 or TAZ/TEAD1 partially sensitized LP-1/Cfz cells to carfilzomib. …
Mll3/Mll4 Are Required For Cbp/P300 Binding On Enhancers And Super-Enhancer Formation In Brown Adipogenesis., Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge
Mll3/Mll4 Are Required For Cbp/P300 Binding On Enhancers And Super-Enhancer Formation In Brown Adipogenesis., Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge
Anatomy and Regenerative Biology Faculty Publications
Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes in cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ), coactivator MED1, RNA polymerase II, as well as epigenome (H3K4me1/2/3, H3K9me2, H3K27me3, H3K36me3, H3K27ac), transcriptome and chromatin opening during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT). We show that MLL4 and CBP drive the dynamic enhancer epigenome, which correlates with the dynamic transcriptome. MLL3/MLL4 are required for CBP/p300 binding on enhancers activated during adipogenesis. Further, MLL4 …
Dbvar Structural Variant Cluster Set For Data Analysis And Variant Comparison, Ben Busby, Lon Phan, Jeffrey Hsu, Le Quang Minh Tri, Micheala Willi, Tamer A. Mansour, Yan Kai, John R. Garner, John R. Lopez
Dbvar Structural Variant Cluster Set For Data Analysis And Variant Comparison, Ben Busby, Lon Phan, Jeffrey Hsu, Le Quang Minh Tri, Micheala Willi, Tamer A. Mansour, Yan Kai, John R. Garner, John R. Lopez
Anatomy and Regenerative Biology Faculty Publications
dbVar houses over 3 million submitted structural variants (SSV) from 120 human studies including copy number variations (CNV), insertions, deletions, inversions, translocations, and complex chromosomal rearrangements. Users can submit multiple SSVs to dbVAR that are presumably identical, but were ascertained by different platforms and samples, to calculate whether the variant is rare or common in the population and allow for cross validation. However, because SSV genomic location reporting can vary – including fuzzy locations where the start and/or end points are not precisely known – analysis, comparison, annotation, and reporting of SSVs across studies can be difficult. This project was …
Brd4 Binds To Active Enhancers To Control Cell Identity Gene Induction In Adipogenesis And Myogenesis, Ji-Eun Lee, Young-Kwon Park, Sarah Park, Younghoon Jang, Nicholas Waring, Anup Dey, Keiko Ozato, Binbin Lai, Weiqun Peng, Kai Ge
Brd4 Binds To Active Enhancers To Control Cell Identity Gene Induction In Adipogenesis And Myogenesis, Ji-Eun Lee, Young-Kwon Park, Sarah Park, Younghoon Jang, Nicholas Waring, Anup Dey, Keiko Ozato, Binbin Lai, Weiqun Peng, Kai Ge
Anatomy and Regenerative Biology Faculty Publications
The epigenomic reader Brd4 is an important drug target for cancers. However, its role in cell differentiation and animal development remains largely unclear. Using two conditional knockout mouse strains and derived cells, we demonstrate that Brd4 controls cell identity gene induction and is essential for adipogenesis and myogenesis. Brd4 co-localizes with lineage-determining transcription factors (LDTFs) on active enhancers during differentiation. LDTFs coordinate with H3K4 mono-methyltransferases MLL3/MLL4 (KMT2C/KMT2D) and H3K27 acetyltransferases CBP/p300 to recruit Brd4 to enhancers activated during differentiation. Brd4 deletion prevents the enrichment of Mediator and RNA polymerase II transcription machinery, but not that of LDTFs, MLL3/MLL4-mediated H3K4me1, and …