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Articles 1 - 26 of 26

Full-Text Articles in Cell Biology

Skeletal Characterization Of Smurf2-Deficient Mice And In Vitro Analysis Of Smurf2-Deficient Chondrocytes, Henry Huang, Eric S. Veien, Hong Zhang, David C. Ayers, Jie Song Jan 2016

Skeletal Characterization Of Smurf2-Deficient Mice And In Vitro Analysis Of Smurf2-Deficient Chondrocytes, Henry Huang, Eric S. Veien, Hong Zhang, David C. Ayers, Jie Song

GSBS Student Publications

Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice. However, it is unclear whether Smurf2 is involved in bone and cartilage homeostasis and if it is required for OA pathogenesis. Here we characterized age-related changes in the bone and articular cartilage of Smurf2-deficient (MT) mice by microCT and histology, and examined whether reduced Smurf2 expression affected the severity of OA upon surgical destabilization of the medial meniscus (DMM). Using immature articular chondrocytes (iMAC) from MT and wild-type (WT) mice, we also examined how Smurf2 deficiency affects chondrogenic and catabolic gene ...


A Calcium-Dependent Protease As A Potential Therapeutic Target For Wolfram Syndrome, Simin Lu, Clay F. Semenkovich, Peter A. Greer, Fumihiko Urano Dec 2014

A Calcium-Dependent Protease As A Potential Therapeutic Target For Wolfram Syndrome, Simin Lu, Clay F. Semenkovich, Peter A. Greer, Fumihiko Urano

GSBS Student Publications

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced ...


Morning And Evening Oscillators Cooperate To Reset Circadian Behavior In Response To Light Input, Pallavi Lamba, Diana Wentworth, Patrick Emery, Yong Zhang May 2014

Morning And Evening Oscillators Cooperate To Reset Circadian Behavior In Response To Light Input, Pallavi Lamba, Diana Wentworth, Patrick Emery, Yong Zhang

GSBS Student Publications

Light is a crucial input for circadian clocks. In Drosophila, short light exposure can robustly shift the phase of circadian behavior. The model for this resetting posits that circadian photoreception is cell autonomous: CRYPTOCHROME senses light, binds to TIMELESS (TIM), and promotes its degradation, which is mediated by JETLAG (JET). However, it was recently proposed that interactions between circadian neurons are also required for phase resetting. We identify two groups of neurons critical for circadian photoreception: the morning (M) and the evening (E) oscillators. These neurons work synergistically to reset rhythmic behavior. JET promotes acute TIM degradation cell autonomously in ...


Angiomotins Link F-Actin Architecture To Hippo Pathway Signaling, Sebastian Mana-Capelli, Murugan Paramasivam, Shubham Dutta, Dannel Mccollum May 2014

Angiomotins Link F-Actin Architecture To Hippo Pathway Signaling, Sebastian Mana-Capelli, Murugan Paramasivam, Shubham Dutta, Dannel Mccollum

GSBS Student Publications

The Hippo pathway regulates the transcriptional coactivator YAP to control cell proliferation, organ size, and stem cell maintenance. Multiple factors, such as substrate stiffness, cell density, and G protein-coupled receptor signaling, regulate YAP through their effects on the F-actin cytoskeleton, although the mechanism is not known. Here we show that angiomotin proteins (AMOT130, AMOTL1, and AMOTL2) connect F-actin architecture to YAP regulation. First, we show that angiomotins are required to relocalize YAP to the cytoplasm in response to various manipulations that perturb the actin cytoskeleton. Second, angiomotins associate with F-actin through a conserved F-actin-binding domain, and mutants defective for F-actin ...


Arf4 Is Required For Mammalian Development But Dispensable For Ciliary Assembly, John A. Follit, Jovenal T. San Agustin, Julie A. Jonassen, Tingting Huang, Jaime A. Rivera-Perez, Kimberly D. Tremblay, Gregory J. Pazour Feb 2014

Arf4 Is Required For Mammalian Development But Dispensable For Ciliary Assembly, John A. Follit, Jovenal T. San Agustin, Julie A. Jonassen, Tingting Huang, Jaime A. Rivera-Perez, Kimberly D. Tremblay, Gregory J. Pazour

GSBS Student Publications

The primary cilium is a sensory organelle, defects in which cause a wide range of human diseases including retinal degeneration, polycystic kidney disease and birth defects. The sensory functions of cilia require specific receptors to be targeted to the ciliary subdomain of the plasma membrane. Arf4 has been proposed to sort cargo destined for the cilium at the Golgi complex and deemed a key regulator of ciliary protein trafficking. In this work, we show that Arf4 binds to the ciliary targeting sequence (CTS) of fibrocystin. Knockdown of Arf4 indicates that it is not absolutely required for trafficking of the fibrocystin ...


Smurf2 Regulates Hematopoietic Stem Cell Self-Renewal And Aging, Charusheila Ramkumar, Yahui Kong, Sally E. Trabucco, Rachel M. Gerstein, Hong Zhang Feb 2014

Smurf2 Regulates Hematopoietic Stem Cell Self-Renewal And Aging, Charusheila Ramkumar, Yahui Kong, Sally E. Trabucco, Rachel M. Gerstein, Hong Zhang

GSBS Student Publications

The age-dependent decline in the self-renewal capacity of stem cells plays a critical role in aging, but the precise mechanisms underlying this decline are not well understood. By limiting proliferative capacity, senescence is thought to play an important role in age-dependent decline of stem cell self-renewal, although direct evidence supporting this hypothesis is largely lacking. We have previously identified the E3 ubiquitin ligase Smurf2 as a critical regulator of senescence. In this study, we found that mice deficient in Smurf2 had an expanded hematopoietic stem cell (HSC) compartment in bone marrow under normal homeostatic conditions, and this expansion was associated ...


The Long Noncoding Rna Thril Regulates Tnfalpha Expression Through Its Interaction With Hnrnpl, Zhonghan Li, Ti-Chun Chao, Kung-Yen Chang, Nianwei Lin, Veena S. Patil, Chisato Shimizu, Steven R. Head, Jane C. Burns, Tariq M. Rana Jan 2014

The Long Noncoding Rna Thril Regulates Tnfalpha Expression Through Its Interaction With Hnrnpl, Zhonghan Li, Ti-Chun Chao, Kung-Yen Chang, Nianwei Lin, Veena S. Patil, Chisato Shimizu, Steven R. Head, Jane C. Burns, Tariq M. Rana

GSBS Student Publications

Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNFalpha expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of ...


Functional Overlap Among Distinct G1/S Inhibitory Pathways Allows Robust G1 Arrest By Yeast Mating Pheromones, Patricia A. Pope, Peter M. Pryciak Dec 2013

Functional Overlap Among Distinct G1/S Inhibitory Pathways Allows Robust G1 Arrest By Yeast Mating Pheromones, Patricia A. Pope, Peter M. Pryciak

GSBS Student Publications

In budding yeast, mating pheromones arrest the cell cycle in G1 phase via a pheromone-activated Cdk-inhibitor (CKI) protein, Far1. Alternate pathways must also exist, however, because deleting the cyclin CLN2 restores pheromone arrest to far1 cells. Here we probe whether these alternate pathways require the G1/S transcriptional repressors Whi5 and Stb1 or the CKI protein Sic1, whose metazoan analogues (Rb or p27) antagonize cell cycle entry. Removing Whi5 and Stb1 allows partial escape from G1 arrest in far1 cln2 cells, along with partial derepression of G1/S genes, which implies a repressor-independent route for inhibiting G1/S transcription. This ...


Crosstalk Between Casein Kinase Ii And Ste20-Related Kinase Nak1, Lubos Cipak, Sneha Gupta, Iva Rajovic, Quan-Wen Jin, Dorothea Anrather, Gustav Ammerer, Dannel Mccollum, Juraj Gregan Mar 2013

Crosstalk Between Casein Kinase Ii And Ste20-Related Kinase Nak1, Lubos Cipak, Sneha Gupta, Iva Rajovic, Quan-Wen Jin, Dorothea Anrather, Gustav Ammerer, Dannel Mccollum, Juraj Gregan

GSBS Student Publications

Although the sterile 20 (Ste20) serine/threonine protein kinase was originally identified as a component of the S. cerevisiae mating pathway, it has homologs in higher eukaryotes and is part of a larger family of Ste20-like kinases. Ste20-like kinases are involved in multiple cellular processes, such as cell growth, morphogenesis, apoptosis and immune response. Carrying out such a diverse array of biological functions requires numerous regulatory inputs and outputs in the form of protein-protein interactions and post-translational modifications. Hence, a thorough knowledge of Ste20-like kinase binding partners and phosphorylation sites will be essential for understanding the various roles of these ...


Multiplying Madly: Deacetylases Take Charge Of Centrosome Duplication And Amplification, Hui-Fang Hung, Heidi Hehnly, Stephen J. Doxsey Dec 2012

Multiplying Madly: Deacetylases Take Charge Of Centrosome Duplication And Amplification, Hui-Fang Hung, Heidi Hehnly, Stephen J. Doxsey

GSBS Student Publications

Comment on: Ling H, et al. Cell Cycle 2012; 11:3779–91; PMID:23022877; http://0-dx.doi.org.library.simmons.edu/10.4161/cc.21985


Screening For Melanoma Modifiers Using A Zebrafish Autochthonous Tumor Model, Sharanya Iyengar, Yariv Houvras, Craig J. Ceol Nov 2012

Screening For Melanoma Modifiers Using A Zebrafish Autochthonous Tumor Model, Sharanya Iyengar, Yariv Houvras, Craig J. Ceol

GSBS Student Publications

Genomic studies of human cancers have yielded a wealth of information about genes that are altered in tumors. A challenge arising from these studies is that many genes are altered, and it can be difficult to distinguish genetic alterations that drove tumorigenesis from that those arose incidentally during transformation. To draw this distinction it is beneficial to have an assay that can quantitatively measure the effect of an altered gene on tumor initiation and other processes that enable tumors to persist and disseminate. Here we present a rapid means to screen large numbers of candidate melanoma modifiers in zebrafish using ...


Epigenetic Control Of Cell Cycle-Dependent Histone Gene Expression Is A Principal Component Of The Abbreviated Pluripotent Cell Cycle, Ricardo F. Medina, Prachi N. Ghule, Fernando Cruzat, Ahmet Rasim Barutcu, Martin A. Montecino, Janet L. Stein, Andre J. Van Wijnen, Gary S. Stein Oct 2012

Epigenetic Control Of Cell Cycle-Dependent Histone Gene Expression Is A Principal Component Of The Abbreviated Pluripotent Cell Cycle, Ricardo F. Medina, Prachi N. Ghule, Fernando Cruzat, Ahmet Rasim Barutcu, Martin A. Montecino, Janet L. Stein, Andre J. Van Wijnen, Gary S. Stein

GSBS Student Publications

Self-renewal of human pluripotent embryonic stem cells proceeds via an abbreviated cell cycle with a shortened G(1) phase. We examined which genes are modulated in this abbreviated period and the epigenetic mechanisms that control their expression. Accelerated upregulation of genes encoding histone proteins that support DNA replication is the most prominent gene regulatory program at the G(1)/S-phase transition in pluripotent cells. Expedited expression of histone genes is mediated by a unique chromatin architecture reflected by major nuclease hypersensitive sites, atypical distribution of epigenetic histone marks, and a region devoid of histone octamers. We observed remarkable differences in ...


Systematic Dissection Of Roles For Chromatin Regulators In A Yeast Stress Response, Assaf Weiner, Hsiuyi V. Chen, Chih Long Liu, Ayelet Rahat, Avital Klien, Luis Soares, Mohanram Gudipati, Jenna Pfeffner, Aviv Regev, Stephen Buratowski, Jeffrey A. Pleiss, Nir Friedman, Oliver J. Rando Jul 2012

Systematic Dissection Of Roles For Chromatin Regulators In A Yeast Stress Response, Assaf Weiner, Hsiuyi V. Chen, Chih Long Liu, Ayelet Rahat, Avital Klien, Luis Soares, Mohanram Gudipati, Jenna Pfeffner, Aviv Regev, Stephen Buratowski, Jeffrey A. Pleiss, Nir Friedman, Oliver J. Rando

GSBS Student Publications

Packaging of eukaryotic genomes into chromatin has wide-ranging effects on gene transcription. Curiously, it is commonly observed that deletion of a global chromatin regulator affects expression of only a limited subset of genes bound to or modified by the regulator in question. However, in many single-gene studies it has become clear that chromatin regulators often do not affect steady-state transcription, but instead are required for normal transcriptional reprogramming by environmental cues. We therefore have systematically investigated the effects of 83 histone mutants, and 119 gene deletion mutants, on induction/repression dynamics of 170 transcripts in response to diamide stress in ...


Scalable Functional Bone Substitutes: Strategic Integration Of Key Structural Elements Of Bone In Synthetic Biomaterials, Tera M. Filion, Jie Song Aug 2011

Scalable Functional Bone Substitutes: Strategic Integration Of Key Structural Elements Of Bone In Synthetic Biomaterials, Tera M. Filion, Jie Song

GSBS Student Publications

Summary: Introduces recent advances in the evolvement of non-metallic orthopedic biomaterials in the design of organic-inorganic composite bone substitutes.


The Mitosis-To-Interphase Transition Is Coordinated By Cross Talk Between The Sin And Mor Pathways In Schizosaccharomyces Pombe, Samriddha Ray, Kazunori Kume, Sneha Gupta, Wanzhong Ge, Mohan Balasubramanian, Dai Hirata, Dannel Mccollum Sep 2010

The Mitosis-To-Interphase Transition Is Coordinated By Cross Talk Between The Sin And Mor Pathways In Schizosaccharomyces Pombe, Samriddha Ray, Kazunori Kume, Sneha Gupta, Wanzhong Ge, Mohan Balasubramanian, Dai Hirata, Dannel Mccollum

GSBS Student Publications

The mechanisms that regulate cytoskeletal remodeling during the transition between mitosis and interphase are poorly understood. In fission yeast the MOR pathway promotes actin polarization to cell tips in interphase, whereas the SIN signaling pathway drives actomyosin ring assembly and cytokinesis. We show that the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase-mediated activation of the most downstream MOR component, the NDR family kinase Orb6. Inactivation of the MOR may be a key function of the SIN because attenuation of MOR signaling rescued the cytokinetic defects of SIN mutants and allowed weak SIN signaling to trigger ectopic ...


Gene Associations: True Romance Or Chance Meeting In A Nuclear Neighborhood, Jeanne B. Lawrence, Christine Moulton Clemson Sep 2008

Gene Associations: True Romance Or Chance Meeting In A Nuclear Neighborhood, Jeanne B. Lawrence, Christine Moulton Clemson

GSBS Student Publications

Many recent studies have raised interest in the nuclear associations of coregulated genes from different chromosomes, often evoking interpretations of gene-gene interactions, communication, and even "romance." However, in some cases, the associations may be indirect and infrequent and may reflect the segregation of active and inactive genes into different nuclear compartments. The study by Brown et al. (see p. 1083 of this issue) reports that the apparent association of erythroid genes is not a direct interaction nor colocalization to one tiny transcription factory but arises as a result of the known clustering of many active genes with larger splicing factor-rich ...


A Screen For Nuclear Transcripts Identifies Two Linked Noncoding Rnas Associated With Sc35 Splicing Domains, John N. Hutchinson, Alexander W. Ensminger, Christine Moulton Clemson, Christopher R. Lynch, Jeanne B. Lawrence, Andrew Chess Feb 2007

A Screen For Nuclear Transcripts Identifies Two Linked Noncoding Rnas Associated With Sc35 Splicing Domains, John N. Hutchinson, Alexander W. Ensminger, Christine Moulton Clemson, Christopher R. Lynch, Jeanne B. Lawrence, Andrew Chess

GSBS Student Publications

BACKGROUND: Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment.

RESULTS: This screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11: NEAT1, a noncoding RNA from ...


Cell Cycle Progression And De Novo Centriole Assembly After Centrosomal Removal In Untransformed Human Cells, Yumi Uetake, Jadranka Loncarek, Joshua J. Nordberg, Christopher N. English, Sabrina La Terra, Alexey Khodjakov, Greenfield Sluder Jan 2007

Cell Cycle Progression And De Novo Centriole Assembly After Centrosomal Removal In Untransformed Human Cells, Yumi Uetake, Jadranka Loncarek, Joshua J. Nordberg, Christopher N. English, Sabrina La Terra, Alexey Khodjakov, Greenfield Sluder

GSBS Student Publications

How centrosome removal or perturbations of centrosomal proteins leads to G1 arrest in untransformed mammalian cells has been a mystery. We use microsurgery and laser ablation to remove the centrosome from two types of normal human cells. First, we find that the cells assemble centrioles de novo after centrosome removal; thus, this phenomenon is not restricted to transformed cells. Second, normal cells can progress through G1 in its entirety without centrioles. Therefore, the centrosome is not a necessary, integral part of the mechanisms that drive the cell cycle through G1 into S phase. Third, we provide evidence that centrosome loss ...


The Protein Arginine Methyltransferase Prmt5 Is Required For Myogenesis Because It Facilitates Atp-Dependent Chromatin Remodeling, Caroline S. Dacwag, Yasuyuki Ohkawa, Sharmistha Pal, Said Sif, Anthony N. Imbalzano Jan 2007

The Protein Arginine Methyltransferase Prmt5 Is Required For Myogenesis Because It Facilitates Atp-Dependent Chromatin Remodeling, Caroline S. Dacwag, Yasuyuki Ohkawa, Sharmistha Pal, Said Sif, Anthony N. Imbalzano

GSBS Student Publications

Skeletal muscle differentiation requires the coordinated activity of transcription factors, histone modifying enzymes, and ATP-dependent chromatin remodeling enzymes. The type II protein arginine methyltransferase Prmt5 symmetrically dimethylates histones H3 and H4 and numerous nonchromatin proteins, and prior work has implicated Prmt5 in transcriptional repression. Here we demonstrate that MyoD-induced muscle differentiation requires Prmt5. One of the first genes activated during differentiation encodes the myogenic regulator myogenin. Prmt5 and dimethylated H3R8 (histone 3 arginine 8) are localized at the myogenin promoter in differentiating cells. Modification of H3R8 required Prmt5, and reduction of Prmt5 resulted in the abrogation of promoter binding by ...


Myod Targets Chromatin Remodeling Complexes To The Myogenin Locus Prior To Forming A Stable Dna-Bound Complex, Ivana L. De La Serna, Yasuyuki Ohkawa, Charlotte A. Berkes, Donald A. Bergstrom, Caroline S. Dacwag, Stephen J. Tapscott, Anthony N. Imbalzano May 2005

Myod Targets Chromatin Remodeling Complexes To The Myogenin Locus Prior To Forming A Stable Dna-Bound Complex, Ivana L. De La Serna, Yasuyuki Ohkawa, Charlotte A. Berkes, Donald A. Bergstrom, Caroline S. Dacwag, Stephen J. Tapscott, Anthony N. Imbalzano

GSBS Student Publications

The activation of muscle-specific gene expression requires the coordinated action of muscle regulatory proteins and chromatin-remodeling enzymes. Microarray analysis performed in the presence or absence of a dominant-negative BRG1 ATPase demonstrated that approximately one-third of MyoD-induced genes were highly dependent on SWI/SNF enzymes. To understand the mechanism of activation, we performed chromatin immunoprecipitations analyzing the myogenin promoter. We found that H4 hyperacetylation preceded Brg1 binding in a MyoD-dependent manner but that MyoD binding occurred subsequent to H4 modification and Brg1 interaction. In the absence of functional SWI/SNF enzymes, muscle regulatory proteins did not bind to the myogenin promoter ...


Disruption Of Ini1 Leads To Peri-Implantation Lethality And Tumorigenesis In Mice, Cynthia J. Guidi, Arthur T. Sands, Brian P. Zambrowicz, Tod K. Turner, Delia A. Demers, William Webster, Thomas W. Smith, Anthony N. Imbalzano, Stephen N. Jones Apr 2001

Disruption Of Ini1 Leads To Peri-Implantation Lethality And Tumorigenesis In Mice, Cynthia J. Guidi, Arthur T. Sands, Brian P. Zambrowicz, Tod K. Turner, Delia A. Demers, William Webster, Thomas W. Smith, Anthony N. Imbalzano, Stephen N. Jones

GSBS Student Publications

SNF5/INI1 is a component of the ATP-dependent chromatin remodeling enzyme family SWI/SNF. Germ line mutations of INI1 have been identified in children with brain and renal rhabdoid tumors, indicating that INI1 is a tumor suppressor. Here we report that disruption of Ini1 expression in mice results in early embryonic lethality. Ini1-null embryos die between 3.5 and 5.5 days postcoitum, and Ini1-null blastocysts fail to hatch, form the trophectoderm, or expand the inner cell mass when cultured in vitro. Furthermore, we report that approximately 15% of Ini1-heterozygous mice present with tumors, mostly undifferentiated or poorly differentiated sarcomas ...


Mammalian Swi-Snf Complexes Contribute To Activation Of The Hsp70 Gene, Ivana L. De La Serna, Kerri A. Carlson, David A. Hill, Cynthia J. Guidi, Ryan O. Stephenson, Said Sif, Robert E. Kingston, Anthony N. Imbalzano Mar 2000

Mammalian Swi-Snf Complexes Contribute To Activation Of The Hsp70 Gene, Ivana L. De La Serna, Kerri A. Carlson, David A. Hill, Cynthia J. Guidi, Ryan O. Stephenson, Said Sif, Robert E. Kingston, Anthony N. Imbalzano

GSBS Student Publications

ATP-dependent chromatin-remodeling complexes are conserved among all eukaryotes and function by altering nucleosome structure to allow cellular regulatory factors access to the DNA. Mammalian SWI-SNF complexes contain either of two highly conserved ATPase subunits: BRG1 or BRM. To identify cellular genes that require mammalian SWI-SNF complexes for the activation of gene expression, we have generated cell lines that inducibly express mutant forms of the BRG1 or BRM ATPases that are unable to bind and hydrolyze ATP. The mutant subunits physically associate with at least two endogenous members of mammalian SWI-SNF complexes, suggesting that nonfunctional, dominant negative complexes may be formed ...


Stabilization And Localization Of Xist Rna Are Controlled By Separate Mechanisms And Are Not Sufficient For X Inactivation, Christine Moulton Clemson, Jennifer C. Chow, Carolyn J. Brown, Jeanne B. Lawrence Jul 1998

Stabilization And Localization Of Xist Rna Are Controlled By Separate Mechanisms And Are Not Sufficient For X Inactivation, Christine Moulton Clemson, Jennifer C. Chow, Carolyn J. Brown, Jeanne B. Lawrence

GSBS Student Publications

These studies address whether XIST RNA is properly localized to the X chromosome in somatic cells where human XIST expression is reactivated, but fails to result in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935-2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST RNA does not localize in reactivants or in naturally inactive human X chromosomes in mouse/ human hybrid cells. The XIST transcripts are fully stabilized despite their inability to localize, and hence XIST RNA localization can be uncoupled from stabilization, indicating that these are separate steps controlled by ...


Xist Rna Paints The Inactive X Chromosome At Interphase: Evidence For A Novel Rna Involved In Nuclear/Chromosome Structure, Christine Moulton Clemson, John A. Mcneil, Huntington F. Willard, Jeanne B. Lawrence Feb 1996

Xist Rna Paints The Inactive X Chromosome At Interphase: Evidence For A Novel Rna Involved In Nuclear/Chromosome Structure, Christine Moulton Clemson, John A. Mcneil, Huntington F. Willard, Jeanne B. Lawrence

GSBS Student Publications

The XIST gene is implicated in X chromosome inactivation, yet the RNA contains no apparent open reading frame. An accumulation of XIST RNA is observed near its site of transcription, the inactive X chromosome (Xi). A series of molecular cytogenetic studies comparing properties of XIST RNA to other protein coding RNAs, support a critical distinction for XIST RNA; XIST does not concentrate at Xi simply because it is transcribed and processed there. Most notably, morphometric and 3-D analysis reveals that XIST RNA and Xi are coincident in 2- and 3-D space; hence, the XIST RNA essentially paints Xi. Several results ...


Nonrandom Gene Organization: Structural Arrangements Of Specific Pre-Mrna Transcription And Splicing With Sc-35 Domains, Yigong P. Xing, Carol V. Johnson, Phillip T. Moen, John A. Mcneil, Jeanne B. Lawrence Dec 1995

Nonrandom Gene Organization: Structural Arrangements Of Specific Pre-Mrna Transcription And Splicing With Sc-35 Domains, Yigong P. Xing, Carol V. Johnson, Phillip T. Moen, John A. Mcneil, Jeanne B. Lawrence

GSBS Student Publications

This work demonstrates a highly nonrandom distribution of specific genes relative to nuclear domains enriched in splicing factors and poly(A)+ RNA, and provides evidence for the direct involvement of these in pre-mRNA metabolism. As investigated in hundreds of diploid fibroblasts, human collagen I alpha 1 and beta-actin DNA/RNA showed a very high degree of spatial association with SC-35 domains, whereas three nontranscribed genes, myosin heavy chain, neurotensin, and albumin, showed no such preferential association. Collagen I alpha 1 RNA accumulates within the more central region of the domain, whereas beta-actin RNA localizes at the periphery. A novel approach ...


Preservation Of Specific Rna Distribution Within The Chromatin-Depleted Nuclear Substructure Demonstrated By In Situ Hybridization Coupled With Biochemical Fractionation, Yigong P. Xing, Jeanne B. Lawrence Mar 1991

Preservation Of Specific Rna Distribution Within The Chromatin-Depleted Nuclear Substructure Demonstrated By In Situ Hybridization Coupled With Biochemical Fractionation, Yigong P. Xing, Jeanne B. Lawrence

GSBS Student Publications

Biochemical fractionation procedures previously shown to remove 95% of cellular protein, DNA, and phospholipid, were combined with fluorescence in situ hybridization to provide a critical evaluation of the retention and spatial preservation of specific primary transcripts within the chromatin-depleted nuclear substructure, operationally defined as the nuclear "matrix." This unique approach made it possible to directly address whether nuclear extraction procedures preserve, create, or destroy ribonucleoprotein filament structures. Comparison of nuclei before and after fractionation demonstrated that localized foci or "tracks" of specific nRNA are unambiguously retained in the nuclear matrix preparation. Two well-characterized nuclear fractionation procedures were used and three ...