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Full-Text Articles in Cell Biology

Diabetes Impairs Wound Healing By Dnmt1-Dependent Dysregulation Of Hematopoietic Stem Cells Differentiation Towards Macrophages, Jinglian Yan, Guodong Tie, Shoying Wang, Amanda A. Tutto, Natale Demarco, Lyne Khair, Thomas G. Fazzio, Louis M. Messina Jan 2018

Diabetes Impairs Wound Healing By Dnmt1-Dependent Dysregulation Of Hematopoietic Stem Cells Differentiation Towards Macrophages, Jinglian Yan, Guodong Tie, Shoying Wang, Amanda A. Tutto, Natale Demarco, Lyne Khair, Thomas G. Fazzio, Louis M. Messina

Open Access Articles

People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU.1, and Klf4 ...


Large Family Cohorts Of Lymphoblastoid Cells Provide A New Cellular Model For Investigating Facioscapulohumeral Muscular Dystrophy, Takako I. Jones, Charis L. Himeda, Daniel P. Perez, Peter L. Jones Mar 2017

Large Family Cohorts Of Lymphoblastoid Cells Provide A New Cellular Model For Investigating Facioscapulohumeral Muscular Dystrophy, Takako I. Jones, Charis L. Himeda, Daniel P. Perez, Peter L. Jones

Open Access Articles

Facioscapulohumeral muscular dystrophy (FSHD) is associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite repeat. The resulting DNA hypomethylation and relaxation of epigenetic repression leads to increased expression of the deleterious DUX4-fl mRNA encoded within the distal D4Z4 repeat. With the typical late onset of muscle weakness, prevalence of asymptomatic individuals, and an autosomal dominant mode of inheritance, FSHD is often passed on from one generation to the next and affects multiple individuals within a family. Here we have characterized unique collections of 114 lymphoblastoid cell lines (LCLs) generated from 12 multigenerational FSHD families, including 56 LCLs from ...


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 ...