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Articles 1 - 9 of 9

Full-Text Articles in Cell Biology

Roles Of Euchromatin And Heterochromatin In Hepatocyte Maturation And Liver Fibrosis, Jessica Mae Grindheim Jan 2019

Roles Of Euchromatin And Heterochromatin In Hepatocyte Maturation And Liver Fibrosis, Jessica Mae Grindheim

Publicly Accessible Penn Dissertations

Liver transplantation is the main treatment for acute liver failure patients; however, there is an insufficient supply of donor livers. Since transplanting hepatocytes, the main liver cell type, provides therapeutic effect and can be a bridge to transplant or recovery, scientists are working on generating replacement hepatocytes from stem cells and other cell types through reprogramming protocols. Currently, replacement hepatocytes recapitulate a subset of natural hepatocyte features, yet are still in an immature state, as they have not silenced all immature hepatocyte genes and activated all mature hepatocyte genes. Consequently, replacement hepatocytes do not perform as well as natural hepatocytes ...


Tale Factors Use Two Distinct Functional Modes To Control An Essential Zebrafish Gene Expression Program, Franck Ladam, William Stanney, Ian J. Donaldson, Ozge Yildiz, Nicoletta Bobola, Charles G. Sagerstrom Jun 2018

Tale Factors Use Two Distinct Functional Modes To Control An Essential Zebrafish Gene Expression Program, Franck Ladam, William Stanney, Ian J. Donaldson, Ozge Yildiz, Nicoletta Bobola, Charles G. Sagerstrom

Open Access Articles

TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN ...


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 ...


Gcn5 Impacts Fgf Signaling At Multiple Levels And Activates C-Myc Target Genes During Early Differentiation Of Embryoid Bodies, Li Wang Aug 2017

Gcn5 Impacts Fgf Signaling At Multiple Levels And Activates C-Myc Target Genes During Early Differentiation Of Embryoid Bodies, Li Wang

UT GSBS Dissertations and Theses (Open Access)

Precise control of gene expression during development is orchestrated by transcription factors, signaling pathways and co-regulators, with complex cross-regulatory events often occurring. Growing evidence has identified chromatin modifiers as important regulators for development as well, yet how particular chromatin modifying enzymes affect specific developmental processes remains largely unclear. Embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the abilities to generate almost all cell types in adult tissues. The dual capacity of ESCs to self-renew and differentiate offers unlimited potential for studying gene regulation events at specific developmental stages in vitro that parallel developmental events during embryogenesis in vivo.

In ...


Kat-Independent Gene Regulation By Tip60 Promotes Esc Self-Renewal But Not Pluripotency, Diwash Acharya, Sarah J. Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A. Rivera-Perez, Thomas G. Fazzio Apr 2017

Kat-Independent Gene Regulation By Tip60 Promotes Esc Self-Renewal But Not Pluripotency, Diwash Acharya, Sarah J. Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A. Rivera-Perez, Thomas G. Fazzio

Pediatric Publications and Presentations

Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a KAT-dependent function ...


Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski Dec 2016

Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski

GSBS Dissertations and Theses

Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational ...


Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio Nov 2016

Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio

Open Access Articles

Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that ...


Function And Regulation Of The Tip60-P400 Complex In Embryonic Stem Cells: A Dissertation, Poshen B. Chen Aug 2015

Function And Regulation Of The Tip60-P400 Complex In Embryonic Stem Cells: A Dissertation, Poshen B. Chen

GSBS Dissertations and Theses

The following work examines the mechanisms by which Tip60-p400 chromatin remodeling complex regulates gene expression in embryonic stem cells (ESCs). Tip60-p400 complex has distinct functions in undifferentiated and differentiated cells. While Tip60-p400 is often associated with gene activation in differentiated cells, its most prominent function in ESCs is to repress differentiation-related genes. I show that Tip60-p400 interacts with Hdac6 and other proteins to form a unique form of the complex in ESCs. Tip60-Hdac6 interaction is stem cell specific and is necessary for Tip60-p400 mediated gene regulation, indicating that Tip60- p400 function is controlled in part through the regulation of Hdac6 ...


Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip Jul 2014

Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip

UMass Center for Clinical and Translational Science Supported Publications

Intestinal stem cells (ISCs) in the adult Drosophila midgut can respond to tissue damage and support repair. We used genetic manipulation to increase the number of ISC-like cells in the adult midgut and performed gene expression profiling to identify potential ISC regulators. A detailed analysis of one of these potential regulators, the zinc-finger protein Charlatan, was carried out. MARCM clonal analysis and RNAi in precursor cells showed that loss of Chn function caused severe ISC division defects, including loss of EdU incorporation, phosphorylated histone 3 staining and expression of the mitotic protein Cdc2. Loss of Charlatan also led to a ...