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Articles 1 - 11 of 11

Full-Text Articles in Cell Biology

Optimization Of Transcription Factor Binding Map Accuracy Utilizing Knockout-Mouse Models, Wolfgang Krebs, Susanne V. Schmidt, Alon Goren, Dominic De Nardo, Larisa Labzin, Anton Bovier, Thomas Ulas, Heidi Theis, Michael Kraut, Eicke Latz, Marc Beyer, Joachim L. Schultze Dec 2014

Optimization Of Transcription Factor Binding Map Accuracy Utilizing Knockout-Mouse Models, Wolfgang Krebs, Susanne V. Schmidt, Alon Goren, Dominic De Nardo, Larisa Labzin, Anton Bovier, Thomas Ulas, Heidi Theis, Michael Kraut, Eicke Latz, Marc Beyer, Joachim L. Schultze

Open Access Articles

Genome-wide assessment of protein-DNA interaction by chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key technology for studying transcription factor (TF) localization and regulation of gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq studies depend on many variables, including antibody affinity and specificity. Thus far, efforts to improve antibody reagents for ChIP-seq experiments have focused mainly on generating higher quality antibodies. Here we introduce KOIN (knockout implemented normalization) as a novel strategy to increase signal specificity and reduce noise by using TF knockout mice as a critical control for ChIP-seq data experiments. Additionally, KOIN can identify 'hyper ChIPable ...


Two Ways To Fold The Genome During The Cell Cycle: Insights Obtained With Chromosome Conformation Capture, Job Dekker Nov 2014

Two Ways To Fold The Genome During The Cell Cycle: Insights Obtained With Chromosome Conformation Capture, Job Dekker

Open Access Articles

Genetic and epigenetic inheritance through mitosis is critical for dividing cells to maintain their state. This process occurs in the context of large-scale re-organization of chromosome conformation during prophase leading to the formation of mitotic chromosomes, and during the reformation of the interphase nucleus during telophase and early G1. This review highlights how recent studies over the last 5 years employing chromosome conformation capture combined with classical models of chromosome organization based on decades of microscopic observations, are providing new insights into the three-dimensional organization of chromatin inside the interphase nucleus and within mitotic chromosomes. One striking observation is that ...


Human Breast Progenitor Cell Numbers Are Regulated By Wnt And Tbx3, Lisa M. Arendt, Jessica St. Laurent, Ania Wronski, Silvia Caballero, Stephen Lyle, Stephen P. Naber, Charlotte Kuperwasser Oct 2014

Human Breast Progenitor Cell Numbers Are Regulated By Wnt And Tbx3, Lisa M. Arendt, Jessica St. Laurent, Ania Wronski, Silvia Caballero, Stephen Lyle, Stephen P. Naber, Charlotte Kuperwasser

Open Access Articles

BACKGROUND: Although human breast development is mediated by hormonal and non-hormonal means, the mechanisms that regulate breast progenitor cell activity remain to be clarified. This limited understanding of breast progenitor cells has been due in part to the lack of appropriate model systems to detect and characterize their properties.

METHODS: To examine the effects of WNT signaling and TBX3 expression on progenitor activity in the breast, primary human mammary epithelial cells (MEC) were isolated from reduction mammoplasty tissues and transduced with lentivirus to overexpress WNT1 or TBX3 or reduce expression of their cognate receptors using shRNA. Changes in progenitor activity ...


Reassessment Of The Role Of Tsc, Mtorc1 And Micrornas In Amino Acids-Meditated Translational Control Of Top Mrnas, Ilona Patursky-Polischuk, Judith Kasir, Rachel Miloslavski, Zvi Hayouka, Mirit Hausner-Hanochi, Miri Stolovich-Rain, Pinchas Tsukerman, Moshe Biton, Rajini R. Mudhasani, Stephen N. Jones, Oded Meyuhas Oct 2014

Reassessment Of The Role Of Tsc, Mtorc1 And Micrornas In Amino Acids-Meditated Translational Control Of Top Mrnas, Ilona Patursky-Polischuk, Judith Kasir, Rachel Miloslavski, Zvi Hayouka, Mirit Hausner-Hanochi, Miri Stolovich-Rain, Pinchas Tsukerman, Moshe Biton, Rajini R. Mudhasani, Stephen N. Jones, Oded Meyuhas

Open Access Articles

TOP mRNAs encode components of the translational apparatus, and repression of their translation comprises one mechanism, by which cells encountering amino acid deprivation downregulate the biosynthesis of the protein synthesis machinery. This mode of regulation involves TSC as knockout of TSC1 or TSC2 rescued TOP mRNAs translation in amino acid-starved cells. The involvement of mTOR in translational control of TOP mRNAs is demonstrated by the ability of constitutively active mTOR to relieve the translational repression of TOP mRNA upon amino acid deprivation. Consistently, knockdown of this kinase as well as its inhibition by pharmacological means blocked amino acid-induced translational activation ...


Modeling T Cell Receptor Recognition Of Cd1-Lipid And Mr1-Metabolite Complexes, Brian G. Pierce, Thom Vreven, Zhiping Weng Sep 2014

Modeling T Cell Receptor Recognition Of Cd1-Lipid And Mr1-Metabolite Complexes, Brian G. Pierce, Thom Vreven, Zhiping Weng

Open Access Articles

BACKGROUND: T cell receptors (TCRs) can recognize diverse lipid and metabolite antigens presented by MHC-like molecules CD1 and MR1, and the molecular basis of many of these interactions has not been determined. Here we applied our protein docking algorithm TCRFlexDock, previously developed to perform docking of TCRs to peptide-MHC (pMHC) molecules, to predict the binding of alphabeta and gammadelta TCRs to CD1 and MR1, starting with the structures of the unbound molecules.

RESULTS: Evaluating against TCR-CD1d complexes with crystal structures, we achieved near-native structures in the top 20 models for two out of four cases, and an acceptable-rated prediction for ...


Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock Aug 2014

Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock

Open Access Articles

When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been ...


A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando Aug 2014

A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando

Open Access Articles

Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states, chromatin insulator function, chromosome folding, and the maintenance of the pluripotent state of embryonic stem cells. Here, we extend a pulse-chase strategy for carrying out genome-wide measurements of histone dynamics to several histone variants in murine embryonic stem cells and somatic tissues, recapitulating expected characteristics of the well characterized H3.3 histone variant. We extended this system to the less-studied MacroH2A2 variant, commonly described as a "repressive" histone variant whose accumulation in chromatin is thought to fix the epigenetic state of differentiated ...


Hsa-Mir-30c Promotes The Invasive Phenotype Of Metastatic Breast Cancer Cells By Targeting Nov/Ccn3, Jason R. Dobson, Hanna Taipaleenmaki, Yu-Jie Hu, Deli Hong, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jitesh Pratap Aug 2014

Hsa-Mir-30c Promotes The Invasive Phenotype Of Metastatic Breast Cancer Cells By Targeting Nov/Ccn3, Jason R. Dobson, Hanna Taipaleenmaki, Yu-Jie Hu, Deli Hong, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jitesh Pratap

Open Access Articles

BACKGROUND: For treatment and prevention of metastatic disease, one of the premier challenges is the identification of pathways and proteins to target for clinical intervention. Micro RNAs (miRNAs) are short, non-coding RNAs, which regulate cellular activities by either mRNA degradation or translational inhibition. Our studies focused on the invasive properties of hsa-mir30c based on its high expression in MDA-MB-231 metastatic cells and our bioinformatic analysis of the Cancer Genome Atlas that identified aberrant hsa-mir-30c to be associated with poor survival.

METHODS: Contributions of hsa-mir-30c to breast cancer cell invasion were examined by Matrigel invasion transwell assays following modulation of hsa-mir-30c ...


To Protect Or Reject, Mary Munson Jun 2014

To Protect Or Reject, Mary Munson

Open Access Articles

A protein known for its role in dismantling faulty SNARE complexes can also help to maintain complexes that have formed properly during membrane fusion.


Genomic Occupancy Of Runx2 With Global Expression Profiling Identifies A Novel Dimension To Control Of Osteoblastogenesis, Hai Wu, Troy W. Whitfield, Jonathan A.R. Gordon, Jason R. Dobson, Phillip W.L. Tai, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian Mar 2014

Genomic Occupancy Of Runx2 With Global Expression Profiling Identifies A Novel Dimension To Control Of Osteoblastogenesis, Hai Wu, Troy W. Whitfield, Jonathan A.R. Gordon, Jason R. Dobson, Phillip W.L. Tai, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian

Open Access Articles

BACKGROUND: Osteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcriptional program essential for bone formation through genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed.

RESULTS: By performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation--proliferation, matrix deposition and mineralization--we identify Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing over the course of these stages, we ...


Pregnancy-Associated Breast Cancers Are Driven By Differences In Adipose Stromal Cells Present During Lactation, Jessica Mccready, Lisa M. Arendt, Eugene Glover, Vandana Iyer, Jerrica L. Briendel, Stephen Lyle, Stephen P. Naber, Daniel G. Jay, Charlotte Kuperwasser Jan 2014

Pregnancy-Associated Breast Cancers Are Driven By Differences In Adipose Stromal Cells Present During Lactation, Jessica Mccready, Lisa M. Arendt, Eugene Glover, Vandana Iyer, Jerrica L. Briendel, Stephen Lyle, Stephen P. Naber, Daniel G. Jay, Charlotte Kuperwasser

Open Access Articles

INTRODUCTION: The prognosis of breast cancer is strongly influenced by the developmental stage of the breast when the tumor is diagnosed. Pregnancy-associated breast cancers (PABCs), cancers diagnosed during pregnancy, lactation, or in the first postpartum year, are typically found at an advanced stage, are more aggressive and have a poorer prognosis. Although the systemic and microenvironmental changes that occur during post-partum involution have been best recognized for their role in the pathogenesis of PABCs, epidemiological data indicate that PABCs diagnosed during lactation have an overall poorer prognosis than those diagnosed during involution. Thus, the physiologic and/or biological events during ...