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1.  CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense non-coding RNA 
Neuron  2011;70(6):1071-1084.
Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder caused by CAG / polyglutamine repeat expansions in the ataxin-7 gene. Ataxin-7 is a component of two different transcription co-activator complexes, and recent work indicates that disease protein normal function is altered in polyglutamine neurodegeneration. Given this, we studied how ataxin-7 gene expression is regulated. The ataxin-7 repeat and translation start site are flanked by binding sites for CTCF, a highly conserved multi-functional transcription regulator. When we analyzed this region, we discovered an adjacent alternative promoter and a convergently transcribed antisense non-coding RNA, SCAANT1. To understand how CTCF regulates ataxin-7 gene expression, we introduced ataxin-7 mini-genes into mice, and found that CTCF is required for SCAANT1 expression. Loss of SCAANT1 de-repressed ataxin-7 sense transcription in a cis-dependent fashion, and was accompanied by chromatin remodeling. Discovery of this pathway underscores the importance of altered epigenetic regulation for disease pathology at repeat loci exhibiting bidirectional transcription.
PMCID: PMC3139428  PMID: 21689595
2.  Blood-Based Detection of Radiation Exposure in Humans Based on Novel Phospho-Smc1 ELISA 
Radiation Research  2010;175(3):266-281.
The structural maintenance of chromosome 1 (Smc1) protein is a member of the highly conserved cohesin complex and is involved in sister chromatid cohesion. In response to ionizing radiation, Smc1 is phosphorylated at two sites, Ser-957 and Ser-966, and these phosphorylation events are dependent on the ATM protein kinase. In this study, we describe the generation of two novel ELISAs for quantifying phospho-Smc1Ser-957 and phospho-Smc1Ser-966. Using these novel assays, we quantify the kinetic and biodosimetric responses of human cells of hematological origin, including immortalized cells, as well as both quiescent and cycling primary human PBMC. Additionally, we demonstrate a robust in vivo response for phospho-Smc1Ser-957 and phospho-Smc1Ser-966 in lymphocytes of human patients after therapeutic exposure to ionizing radiation, including total-body irradiation, partial-body irradiation, and internal exposure to 131I. These assays are useful for quantifying the DNA damage response in experimental systems and potentially for the identification of individuals exposed to radiation after a radiological incident.
PMCID: PMC3123689  PMID: 21388270

Results 1-2 (2)