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Molecular Biology Commons

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Developmental Biology

University of Massachusetts Medical School

2013

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Articles 1 - 6 of 6

Full-Text Articles in Molecular Biology

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 ...


Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio Oct 2013

Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio

Cancer Biology Publications and Presentations

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains ...


The Scaffold Attachment Factor B1 (Safb1) Regulates Myogenic Differentiation By Facilitating The Transition Of Myogenic Gene Chromatin From A Repressed To An Activated State, J. Manuel Hernandez-Hernandez, Chandrashekara Mallappa, Brian T. Nasipak, Steffi Oesterreich, Anthony N. Imbalzano Jun 2013

The Scaffold Attachment Factor B1 (Safb1) Regulates Myogenic Differentiation By Facilitating The Transition Of Myogenic Gene Chromatin From A Repressed To An Activated State, J. Manuel Hernandez-Hernandez, Chandrashekara Mallappa, Brian T. Nasipak, Steffi Oesterreich, Anthony N. Imbalzano

University of Massachusetts Medical School Faculty Publications

The regulation of skeletal muscle gene expression during myogenesis is mediated by lineage-specific transcription factors in combination with numerous cofactors, many of which modify chromatin structure. However, the involvement of scaffolding proteins that organize chromatin and chromatin-associated regulatory proteins has not extensively been explored in myogenic differentiation. Here, we report that Scaffold attachment factor b1 (Safb1), primarily associated with transcriptional repression, functions as a positive regulator of myogenic differentiation. Knockdown of Safb1 inhibited skeletal muscle marker gene expression and differentiation in cultured C2C12 myoblasts. In contrast, over-expression resulted in the premature expression of critical muscle structural proteins and formation of ...


Victor Ambros: The Broad Scope Of Micrornas. Interview By Caitlin Sedwick, Victor R. Ambros May 2013

Victor Ambros: The Broad Scope Of Micrornas. Interview By Caitlin Sedwick, Victor R. Ambros

Program in Molecular Medicine Publications and Presentations

Interview with Victor Ambros, who studies how microRNAs impact development.


Role Of Map4k4 In Skeletal Muscle Differentiation: A Dissertation, Mengxi Wang May 2013

Role Of Map4k4 In Skeletal Muscle Differentiation: A Dissertation, Mengxi Wang

GSBS Dissertations and Theses

Skeletal muscle is a complicated and heterogeneous striated muscle tissue that serves critical mechanical and metabolic functions in the organism. The process of generating skeletal muscle, myogenesis, is elaborately coordinated by members of the protein kinase family, which transmit diverse signals initiated by extracellular stimuli to myogenic transcriptional hierarchy in muscle cells. Mitogen-activated protein kinases (MAPKs) including p38 MAPK, c-Jun N terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) are components of serine/threonine protein kinase cascades that play important roles in skeletal muscle differentiation. The exploration of MAPK upstream kinases identified mitogen activated protein kinase kinase kinase kinase ...


Stress Granules As Crucibles Of Als Pathogenesis, Yun R. Li, Oliver D. King, James Shorter, Aaron D. Gitler Apr 2013

Stress Granules As Crucibles Of Als Pathogenesis, Yun R. Li, Oliver D. King, James Shorter, Aaron D. Gitler

Wellstone Center for FSHD Publications

Amyotrophic lateral sclerosis (ALS) is a fatal human neurodegenerative disease affecting primarily motor neurons. Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS. TDP-43 and FUS and several related RNA-binding proteins harbor aggregation-promoting prion-like domains that allow them to rapidly self-associate. This property is critical for the formation and dynamics of cellular ribonucleoprotein granules, the crucibles of RNA metabolism and homeostasis. Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as ...