We describe gh-throughput stone ping (HiHiMap), a high-throughput imaging method to measure histones and histone posttranslational modifications (PTMs) in single cells. HiHiMap uses imaging-based quantification of DNA and cyclin A to stage individual cells in the cell cycle to determine the levels of histones or histone PTMs in each stage of the cell cycle. As proof of principle, we apply HiHiMap to measure the level of 21 core histones, histone variants, and PTMs in primary, immortalized, and transformed cells.
View Article and Find Full Text PDFTrends Cell Biol
November 2014
Age is a major risk factor for cancer. Alterations in DNA methylation, histone modifications, chromatin structure, and epigenetic regulatory mechanisms are prominent hallmarks of both the aging process and cancer. Intriguingly--or possibly coincidentally--several chromatin features are common between aging and cancer.
View Article and Find Full Text PDFViral expression varies widely between untransformed HTLV-1 positive clones derived from infected individuals without malignancy. Here we show that, in the absence of malignancy, 68% of HTLV-1 positive clones carry deleted (10%) or methylated (58%) 5' LTR. These changes were found to contribute to the fluctuation of viral expression between clones.
View Article and Find Full Text PDFRecent Results Cancer Res
April 2014
Human T-cell lymphotropic virus type 1 (HTLV-1) was originally discovered in the early 1980s. It is the first retrovirus to be unambiguously linked causally to a human cancer. HTLV-1 currently infects approximately 20 million people worldwide.
View Article and Find Full Text PDFBackground: Human T-cell Leukemia Virus type 1 (HTLV-1) infects 20 million individuals world-wide and causes Adult T-cell Leukemia/Lymphoma (ATLL), a highly aggressive T-cell cancer. ATLL is refractory to treatment with conventional chemotherapy and fewer than 10% of afflicted individuals survive more than 5 years after diagnosis. HTLV-1 encodes a viral oncoprotein, Tax, that functions in transforming virus-infected T-cells into leukemic cells.
View Article and Find Full Text PDFHuman T-cell Leukemia Virus type 1 (HTLV-1) and 2 (HTLV-2) are two closely related human retroviruses. HTLV-1 is associated with an aggressive Adult T-cell Leukemia (ATL) while there is no evidence for an association of HTLV-2 with any human malignancies. The two viruses encode transactivator proteins, Tax-1 and Tax-2 respectively.
View Article and Find Full Text PDFAutophagy, a general homeostatic process for degradation of cytosolic proteins or organelles, has been reported to modulate the replication of many viruses. The role of autophagy in human T-cell leukemia virus type 1 (HTLV-1) replication has, however, been uncharacterized. Here, we report that HTLV-1 infection increases the accumulation of autophagosomes and that this accumulation increases HTLV-1 production.
View Article and Find Full Text PDFUntransformed HTLV-1 positive CD4(+) cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting HTLV-1 positive CD4(+) cells cloned from patients, hTERT expression parallels tax expression and cell cycling. Upon activation, these cells dramatically augment tax expression, whereas their increase in telomerase activity is about 20 times lower than that of their uninfected counterpart.
View Article and Find Full Text PDFObjective: Telomeres are protected by tightly regulated factors and elongated by telomerase. Short and/or deprotected chromosomes are recombinogenic and thereby cancer prone.
Materials And Methods: Together with the quantification of telomerase activity (TA), measuring telomere length (TL) and expression of the genes that govern telomere protection and elongation are useful for assessing telomere homeostasis.
Here we investigate the mechanisms by which HTLV-1 infection prevents the cell death of CD8(+) T cells in vivo. We show that upon natural infection, cloned CD8(+) but not CD4(+) cells from patients without malignancy become resistant to Fas-mediated cell death and acquire an antiapoptotic transcriptome that includes the overexpression of cIAP-2 and c-FLIP(L). CD8(+) lymphocyte-restricted cIAP-2 overexpression correlates with resistance to Fas-mediated apoptosis and depends on tax expression via NF-KappaB.
View Article and Find Full Text PDFBackground: Adult T cell leukemia results from the malignant transformation of a CD4+ lymphoid clone carrying an integrated HTLV-1 provirus that has undergone several oncogenic events over a 30-60 year period of persistent clonal expansion. Both CD4+ and CD8+ lymphocytes are infected in vivo; their expansion relies on CD4+ cell cycling and on the prevention of CD8+ cell death. Cloned infected CD4+ but not CD8+ T cells from patients without malignancy also add up nuclear and mitotic defects typical of genetic instability related to the expression of the virus-encoded oncogene tax.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2009
As other deltaretroviruses HTLV-1 replication in vivo includes a first short step of reverse transcription that is followed by the persistent clonal expansion of infected cells. In vivo these cells include the CD4+ and CD8+ lymphocytes yet the virus induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Cloned infected cells from individuals without malignancy possess a dramatic increase in spontaneous proliferation, which predominated with CD8+ lymphocytes and depends on the amount of tax mRNA.
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