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doi:10.1038/sj/leu/2401513

Cited by 4 publications

References 19 publications

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The Role of PML in the Nervous System

Salomoni¹,

Betts-Henderson

2010

Mol Neurobiol

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The promyeloctic leukemia protein PML is a tumor suppressor that was originally identified due to its involvement in the (15;17) translocation of acute promyelocytic leukemia. While the majority of early research has focused upon the role of PML in the pathogenesis of leukemia, more recent evidence has identified important roles for PML in tissues outside the hemopoietic system, including the central nervous system (CNS). Here, we review recent literature on the role of PML in the CNS, with particular focus on the processes of neurodevelopment and neurodegeneration, and propose new lines of investigation.

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The Role of PML in the Nervous System

Salomoni¹,

Betts-Henderson

2010

Mol Neurobiol

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Y chromosome damage underlies testicular abnormalities in ATR-X syndrome

Carlos,

Le,

Garvie

et al. 2023

Preprint

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ATR-X (alpha thalassemia, mental retardation, X-linked) syndrome is a severe developmental disorder affecting males caused by mutations in the chromatin remodelling gene ATRX. Genital abnormalities in affected boys include hypospadias and ambiguous genitalia, and patients show small poorly formed testes with only a few seminiferous tubules. Our mouse model recapitulated these testicular defects when Atrx was specifically deleted in Sertoli cells (ScAtrxKO). ScAtrxKO mice develop small testes with fewer and discontinuous tubules due to G2/M arrest and apoptosis of Sertoli cells. Here, we investigated the mechanism underlying the Sertoli cell defects in ATR-X syndrome. In healthy male control mice, Sertoli cell nuclei contain a single novel 'GATA4 PML nuclear body (NB)' that strongly expresses the transcription factor GATA4, as well as ATRX and its binding partner DAXX. The GATA4 PML NB co-localizes with heterochromatin protein HP1a; and PH3 (a marker of chromosome condensation), and with the short arm of the Y chromosome (Yp). In contrast, ScAtrxKO Sertoli cells contain a single giant GATA4 PML NB, frequently associated with DNA double-strand breaks in G2/M-arrested Sertoli cells that underwent apoptosis. HP1a; and PH3 were absent from the giant GATA4 foci suggesting a local failure in heterochromatin formation and chromosome condensation. Our data indicate that in Sertoli cells, ATRX protects a chromosomal region of Yp from DNA damage, probably during replication stress, and thus protects Sertoli cells from cell death. We discuss Y chromosome damage as a novel mechanism for testicular failure and the potential role of GATA4 during this process.

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An Efficient and Robust Statistical Modeling Approach to Discover Differentially Expressed Genes Using Genomic Expression Profiles

Thomas¹,

Olson²,

Tapscott³

et al. 2001

Genome Res.

287

192

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We have developed a statistical regression modeling approach to discover genes that are differentially expressed between two predefined sample groups in DNA microarray experiments. Our model is based on well-defined assumptions, uses rigorous and well-characterized statistical measures, and accounts for the heterogeneity and genomic complexity of the data. In contrast to cluster analysis, which attempts to define groups of genes and/or samples that share common overall expression profiles, our modeling approach uses known sample group membership to focus on expression profiles of individual genes in a sensitive and robust manner. Further, this approach can be used to test statistical hypotheses about gene expression. To demonstrate this methodology, we compared the expression profiles of 11 acute myeloid leukemia (AML) and 27 acute lymphoblastic leukemia (ALL) samples from a previous study ) and found 141 genes differentially expressed between AML and ALL with a 1% significance at the genomic level. Using this modeling approach to compare different sample groups within the AML samples, we identified a group of genes whose expression profiles correlated with that of thrombopoietin and found that genes whose expression associated with AML treatment outcome lie in recurrent chromosomal locations. Our results are compared with those obtained using t-tests or Wilcoxon rank sum statistics.

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Cited by 4 publications

References 19 publications

The Role of PML in the Nervous System

The Role of PML in the Nervous System

Y chromosome damage underlies testicular abnormalities in ATR-X syndrome

An Efficient and Robust Statistical Modeling Approach to Discover Differentially Expressed Genes Using Genomic Expression Profiles

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