Chromatin modification and epigenetic reprogramming in mammalian development

Li, En

doi:10.1038/nrg887

Cited by 1,718 publications

(1,255 citation statements)

References 127 publications

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“…Epigenetic modulations of DNA and histones determine the pattern of gene expression and silencing (Jaenisch and Bird, 2003). Histone modifications, like de-acetylation of histones by histone deactylases and site-specific methylation of histone H3, may trigger methylation of cytosine residues by methyltransferases (DNMT3a and DNMT3b), which results in gene silencing that is maintained over cell generations by DMNT1 (Li, 2002;Jaenisch and Bird, 2003). The epigenetic regulation of gene expression seems inevitable for multicellular organisms as it underlies the development of cell lineage-specific gene expression and phenotypes from one genotype (Jablonka and Lamb, 1998).…”

Section: Developing New Genomic Research Areasmentioning

confidence: 99%

Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing activities and future possibilities

Beerda

Wyszyńska-Koko

Pas

et al. 2008

Animal

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Subfertility has negative effects for dairy farm profitability, animal welfare and sustainability of animal production. Increasing herd sizes and economic pressures restrict the amount of time that farmers can spend on counteractive management. Genetic improvement will become increasingly important to restore reproductive performance. Complementary to traditional breeding value estimation procedures, genomic selection based on genome-wide information will become more widely applied. Functional genomics, including transcriptomics (gene expression profiling), produces the information to understand the consequences of selection as it helps to unravel physiological mechanisms underlying female fertility traits. Insight into the latter is needed to develop new effective management strategies to combat subfertility. Here, the importance of functional genomics for dairy cow reproduction so far and in the near future is evaluated. Recent gene profiling studies in the field of dairy cow fertility are reviewed and new data are presented on genes that are expressed in the brains of dairy cows and that are involved in dairy cow oestrus (behaviour). Fast-developing new research areas in the field of functional genomics, such as epigenetics, RNA interference, variable copy numbers and nutrigenomics, are discussed including their promising future value for dairy cow fertility.

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Section: Developing New Genomic Research Areasmentioning

confidence: 99%

Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing activities and future possibilities

Beerda

Wyszyńska-Koko

Pas

et al. 2008

Animal

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“…DNMT1 is generally considered to be a maintenance methylase, although it also has de novo methylase activity (Bestor, 2000;Robertson, 2002). Both DNMT3A and DNMT3B catalyse de novo methylation of DNA sequences (Li, 2002). Each of these three enzymes is essential for life, since homozygous knockout alleles of Dnmt1 and Dnmt3b cause embryonic lethality in mice, and mice with homozygous knockout alleles of Dnmt3a die several weeks after birth (Li et al, 1992;Okano et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

et al. 2007

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Cancer cells display an altered distribution of DNA methylation relative to normal cells. Certain tumor suppressor gene promoters are hypermethylated and transcriptionally inactivated, whereas repetitive DNA is hypomethylated and transcriptionally active. Little is understood about how the abnormal DNA methylation patterns of cancer cells are established and maintained. Here, we identify over 20 DNMT3B transcripts from many cancer cell lines and primary acute leukemia cells that contain aberrant splicing at the 5 0 end of the gene, encoding truncated proteins lacking the C-terminal catalytic domain. Many of these aberrant transcripts retain intron sequences. Although the aberrant transcripts represent a minority of the DNMT3B transcripts present, Western blot analysis demonstrates truncated DNMT3B isoforms in the nuclear protein extracts of cancer cells. To test if expression of a truncated DNMT3B protein could alter the DNA methylation patterns within cells, we expressed DNMT3B7, the most frequently expressed aberrant transcript, in 293 cells. DNMT3B7-expressing 293 cells have altered gene expression as identified by microarray analysis. Some of these changes in gene expression correlate with altered DNA methylation of corresponding CpG islands. These results suggest that truncated DNMT3B proteins could play a role in the abnormal distribution of DNA methylation found in cancer cells.

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“…Although histone modification and DNA methylation are both independent processes, they are also integrally linked (27). For example DNA methyltransferases are known to independently recruit histone deacetylases, leading to histone deacetylation and transcriptional repression (28,29).…”

Section: Introductionmentioning

confidence: 99%

DNA demethylation and histone deacetylation inhibition co‐operate to re‐express estrogen receptor beta and induce apoptosis in prostate cancer cell‐lines

et al. 2007

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tom@pelhamcourt.clara.co.uk Introduction Epigenetic silencing mechanisms are increasingly thought to play a major role in the development of human cancers, including prostate cancer. The two major epigenetic regulatory mechanisms involve alterations in DNA methylation and histone acetylation status. Promoter CpG island hypermethylation and histone hypoacetylation, catalysed by DNA methyltransferase (DNMT) and histone deacetylase (HDAC) respectively, are associated with transcriptional repression. Evidence in other cancers suggests the two mechanisms are dynamically linked, yet few studies have examined the potential interaction of the two pathways in prostate cancer. Here we report a synergistic, apoptotic effect of treatment with a demethylating agent and a histone deacetylase inhibitor on cultured prostate cancer cells, with associated re-expression of the putative antiproliferative agent oestrogen receptor beta.Methods LNCaP, DU-145 and PC-3 cells were pre-treated with the DNMT inhibitor 5'-aza-2'-deoxycytidine (5-AZAC) for 72 hours followed by 24 hours combined treatment with 5-AZAC and the HDAC inhibitor trichostatin A (TSA). Following treatment, cells were either processed for cell proliferation, cell toxicity, cell viability and apoptosis assays, or harvested for quantitative real-time RT-PCR gene expression analyses. Assessed target genes were oestrogen receptor beta (ERβ), androgen receptor (AR), progesterone receptor (PGR) and prostate specific antigen (PSA). ResultsIn all cell-lines co-treatment with 5-AZAC and TSA was associated with significantly reduced cell proliferation when compared with control groups (p<0.05); associated reduced cell viability and increased cell death was seen in all cases. Caspase activation was significantly increased in the co-treatment group, indicating that apoptosis was a major mechanism of cell death. Most marked effects were seen in the androgen-dependent, AR-positive LNCaP cell-line. In all cell-lines a marked synergistic re-expression of ERβ was identified in the co-treatment group, a finding which was not seen for either AR or PSA. A similar re-expression of PGR was also identified. ConclusionsAt concentrations associated with gene re-expression, the DNA demethylating agent 5-AZAC and the HDAC inhibitor TSA co-operate in an additive and synergistic way to induce apoptosis in prostate cancer cell-lines. Increased apoptosis in the co-treatment group was associated with marked re-expression of ERβ, which is an intriguing finding, raising the possibility of further targeting of prostate cancer cells with ERβ-selective agents such as phytooestrogens and selective oestrogen receptor modulators (SERMs).

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Chromatin modification and epigenetic reprogramming in mammalian development

Cited by 1,718 publications

References 127 publications

Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing activities and future possibilities

Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing activities and future possibilities

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

DNA demethylation and histone deacetylation inhibition co‐operate to re‐express estrogen receptor beta and induce apoptosis in prostate cancer cell‐lines

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