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

2019

University of Massachusetts Medical School

Cellular and Molecular Physiology

Gene expression

Articles 1 - 4 of 4

Full-Text Articles in Life Sciences

Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano Aug 2019

Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano

Open Access Articles

JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids ...


Rapid Irreversible Transcriptional Reprogramming In Human Stem Cells Accompanied By Discordance Between Replication Timing And Chromatin Compartment, Vishnu Dileep, Rachel Patton Mccord, Job Dekker, David M. Gilbert Jul 2019

Rapid Irreversible Transcriptional Reprogramming In Human Stem Cells Accompanied By Discordance Between Replication Timing And Chromatin Compartment, Vishnu Dileep, Rachel Patton Mccord, Job Dekker, David M. Gilbert

Open Access Articles

The temporal order of DNA replication is regulated during development and is highly correlated with gene expression, histone modifications and 3D genome architecture. We tracked changes in replication timing, gene expression, and chromatin conformation capture (Hi-C) A/B compartments over the first two cell cycles during differentiation of human embryonic stem cells to definitive endoderm. Remarkably, transcriptional programs were irreversibly reprogrammed within the first cell cycle and were largely but not universally coordinated with replication timing changes. Moreover, changes in A/B compartment and several histone modifications that normally correlate strongly with replication timing showed weak correlation during the early ...


Mtf1, A Classic Metal Sensing Transcription Factor, Promotes Myogenesis In Response To Copper, Cristina Tavera-Montañez, Sarah J. Hainer, Daniella Cangussu, Shellaina J. V. Gordon, Yao Xiao, Pablo Reyes-Gutierrez, Anthony N. Imbalzano, Juan G. Navea, Thomas G. Fazzio, Teresita Padilla-Benavides Jun 2019

Mtf1, A Classic Metal Sensing Transcription Factor, Promotes Myogenesis In Response To Copper, Cristina Tavera-Montañez, Sarah J. Hainer, Daniella Cangussu, Shellaina J. V. Gordon, Yao Xiao, Pablo Reyes-Gutierrez, Anthony N. Imbalzano, Juan G. Navea, Thomas G. Fazzio, Teresita Padilla-Benavides

University of Massachusetts Medical School Faculty Publications

MTF1 is a conserved metal-binding transcription factor in eukaryotes that binds to conserved DNA sequence motifs, termed metal response elements (MREs). MTF1 responds to metal excess and deprivation, protects cells from oxidative and hypoxic stresses, and is required for embryonic development in vertebrates. We used multiple strategies to identify an unappreciated role for MTF1 and copper (Cu) in cell differentiation. Upon initiation of myogenesis from primary myoblasts, MTF1 expression increased, as did nuclear localization. Mtf1 knockdown impaired differentiation, while addition of non-toxic concentrations of Cu+ enhanced MTF1 expression and promoted myogenesis. Cu+ bound stoichiometrically to a C-terminus tetra-cysteine of MTF1 ...


Multi-Dimensional Transcriptional Remodeling By Physiological Insulin In Vivo, Thiago M. Batista, Ruben Garcia-Martin, Weikang Cai, Masahiro Konishi, Brian T. O'Neill, Masaji Sakaguchi, Jong Hun Kim, Dae Young Jung, Jason K. Kim, C. Ronald Kahn Mar 2019

Multi-Dimensional Transcriptional Remodeling By Physiological Insulin In Vivo, Thiago M. Batista, Ruben Garcia-Martin, Weikang Cai, Masahiro Konishi, Brian T. O'Neill, Masaji Sakaguchi, Jong Hun Kim, Dae Young Jung, Jason K. Kim, C. Ronald Kahn

Open Access Articles

Regulation of gene expression is an important aspect of insulin action but in vivo is intertwined with changing levels of glucose and counter-regulatory hormones. Here we demonstrate that under euglycemic clamp conditions, physiological levels of insulin regulate interrelated networks of more than 1,000 transcripts in muscle and liver. These include expected pathways related to glucose and lipid utilization, mitochondrial function, and autophagy, as well as unexpected pathways, such as chromatin remodeling, mRNA splicing, and Notch signaling. These acutely regulated pathways extend beyond those dysregulated in mice with chronic insulin deficiency or insulin resistance and involve a broad network of ...