Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 7 of 7

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Temporal Regulation Of Chromatin During Myoblast Differentiation, Akihito Harada, Yasuyuki Ohkawa, Anthony N. Imbalzano Dec 2017

Temporal Regulation Of Chromatin During Myoblast Differentiation, Akihito Harada, Yasuyuki Ohkawa, Anthony N. Imbalzano

UMass Metabolic Network Publications

The commitment to and execution of differentiation programmes involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated. The terminal differentiation of myoblasts to myotubes and mature skeletal muscle is an excellent system to illustrate these points. The ...


A Synthetic Biology Approach To Probing Nucleosome Symmetry, Yuichi Ichikawa, Caitlin M. Connolly, Hsin-Jung Chou, Yuanyuan Chen, Upasna Sharma, Hsuiyi V. Chen, Vineeta Bajaj, Daniel Na. Bolon, Oliver J. Rando, Paul D. Kaufman Sep 2017

A Synthetic Biology Approach To Probing Nucleosome Symmetry, Yuichi Ichikawa, Caitlin M. Connolly, Hsin-Jung Chou, Yuanyuan Chen, Upasna Sharma, Hsuiyi V. Chen, Vineeta Bajaj, Daniel Na. Bolon, Oliver J. Rando, Paul D. Kaufman

UMass Metabolic Network Publications

The repeating subunit of chromatin, the nucleosome, includes two copies of each of the four core histones, and several recent studies have reported that asymmetrically-modified nucleosomes occur at regulatory elements in vivo. To probe the mechanisms by which histone modifications are read out, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, which we extensively validated genetically and biochemically. Comparing the effects of asymmetric histone tail point mutants with those of symmetric double mutants revealed that a single methylated H3K36 per nucleosome was sufficient to silence cryptic transcription in vivo. We also demonstrate the utility of this ...


Quantitative Mass Spectrometry Reveals Changes In Histone H2b Variants As Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation, Matthew Rea, Tingting Jiang, Rebekah Eleazer, Meredith Eckstein, Alan G. Marshall, Yvonne N. Fondufe-Mittendorf May 2016

Quantitative Mass Spectrometry Reveals Changes In Histone H2b Variants As Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation, Matthew Rea, Tingting Jiang, Rebekah Eleazer, Meredith Eckstein, Alan G. Marshall, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here ...


Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen Dec 2015

Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen

GSBS Dissertations and Theses

The following work demonstrates that chromatin regulators play far more pronounced roles in dynamic gene expression than they do in steady-state. Histone modifications have been associated with transcription activity. However, previous analyses of gene expression in mutants affecting histone modifications show limited alteration. I systematically dissected the effects of 83 histone mutants and 119 gene deletion mutants on gene induction/repression in response to diamide stress in yeast. Importantly, I observed far more changes in gene induction/repression than changes in steady-state gene expression. The extensive dynamic gene expression profile of histone mutants and gene deletion mutants also allowed me ...


Chromatin Regulators And Dna Repair: A Dissertation, Gwendolyn M. Bennett Dec 2014

Chromatin Regulators And Dna Repair: A Dissertation, Gwendolyn M. Bennett

GSBS Dissertations and Theses

DNA double-strand break (DSB) repair is essential for maintenance of genome stability. However, the compaction of the eukaryotic genome into chromatin creates an inherent barrier to any DNA-mediated event, such as during DNA repair. This demands that there be mechanisms to modify the chromatin structure and thus access DNA. Recent work has implicated a host of chromatin regulators in the DNA damage response and several functional roles have been defined. Yet the mechanisms that control their recruitment to DNA lesions, and their relationship with concurrent histone modifications, remain unclear. We find that efficient DSB recruitment of many yeast chromatin regulators ...


Hdac6 Regulates Tip60-P400 Function In Stem Cells, Poshen B. Chen, Jui-Hung Hung, Taylor L. Hickman, Andrew H. Coles, James F. Carey, Zhiping Weng, Feixia Chu, Thomas G. Fazzio Dec 2013

Hdac6 Regulates Tip60-P400 Function In Stem Cells, Poshen B. Chen, Jui-Hung Hung, Taylor L. Hickman, Andrew H. Coles, James F. Carey, Zhiping Weng, Feixia Chu, Thomas G. Fazzio

Program in Molecular Medicine Publications and Presentations

In embryonic stem cells (ESCs), the Tip60 histone acetyltransferase activates genes required for proliferation and silences genes that promote differentiation. Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs. Hdac6 is necessary for regulation of most Tip60-p400 target genes, particularly those repressed by the complex. Unlike differentiated cells, where Hdac6 is mainly cytoplasmic, Hdac6 is largely nuclear in ESCs, neural stem cells (NSCs), and some cancer cell lines, and interacts with Tip60-p400 in each. Hdac6 localizes to promoters bound by Tip60-p400 in ESCs, binding downstream of transcription start sites. Surprisingly, Hdac6 does not ...


Brg1, A Swi/Snf Chromatin Remodeling Enzyme Atpase, Is Required For Maintenance Of Nuclear Shape And Integrity, Anthony N. Imbalzano, Karen M. Imbalzano, Jeffrey A. Nickerson Sep 2013

Brg1, A Swi/Snf Chromatin Remodeling Enzyme Atpase, Is Required For Maintenance Of Nuclear Shape And Integrity, Anthony N. Imbalzano, Karen M. Imbalzano, Jeffrey A. Nickerson

Imbalzano Lab Publications

We recently reported that reducing the levels of BRG1, the catalytic subunit of mammalian SWI/SNF chromatin remodeling enzymes, induces alterations in nuclear shape in a breast epithelial cell line. Immunostaining the BRG1 knockdown cells with nuclear lamina antibodies revealed a significantly increased frequency of grooves, or invaginations, in the nuclei. Disruption of each of the major cytoplasmic filament systems (actin, tubulin and cytokeratins) had no impact on the BRG1-dependent changes in nuclear shape, indicating that the observed changes in nuclear morphology are unlikely to be a result of alterations in the integrity of the nuclear-cytoplamic contacts in the cell ...