Pascal Giehr

Pascal Giehr
Ludwig-Maximilians-University of Munich | LMU

Dr.

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29
Publications
3,162
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477
Citations

Publications

Publications (29)
Article
Full-text available
A precise understanding of DNA methylation dynamics is of great importance for a variety of biological processes including cellular reprogramming and differentiation. To date, complex integration of multiple and distinct genome-wide datasets is required to realize this task. We present GwEEP (genome-wide epigenetic efficiency profiling) a versatile...
Article
Full-text available
DNA methylation plays a critical role during development, particularly in repressing retrotransposons. The mammalian methylation landscape is dependent on the combined activities of the canonical maintenance enzyme Dnmt1 and the de novo Dnmts, 3a and 3b. Here, we demonstrate that Dnmt1 displays de novo methylation activity in vitro and in vivo with...
Preprint
Full-text available
Background DNA methylation is an essential epigenetic modification which is set and maintained by DNA methyl transferases (Dnmts) and removed via active and passive mechanisms involving Tet mediated oxidation. While the molecular mechanisms of these enzymes are well studied, their interplay on shaping cell specific methylomes remains less well unde...
Chapter
Full-text available
The understanding of mechanisms that control epigenetic changes is an important research area in modern functional biology. Epigenetic modifications such as DNA methylation are in general very stable over many cell divisions. DNA methylation can however be subject to specific and fast changes over a short time scale even in non-dividing (i.e. not-r...
Article
Full-text available
DNA methylation is an epigenetic mark whose important role in development has been widely recognized. This epigenetic modification results in heritable information not encoded by the DNA sequence. The underlying mechanisms controlling DNA methylation are only partly understood. Several mechanistic models of enzyme activities responsible for DNA met...
Preprint
Full-text available
The understanding of mechanisms that control epigenetic changes is an important research area in modern functional biology. Epigenetic modifications such as DNA methylation are in general very stable over many cell divisions. DNA methylation can however be subject to specific and fast changes over a short time scale even in non-dividing (i.e. not-r...
Article
Full-text available
Pluripotent cells appear to be in a transient state during early development. These cells have the capability to transition into embryonic stem cells (ESCs). It has been reported that mouse pluripotent cells cultivated in chemically defined media sustain the ground state of pluripotency. Because the epigenetic pattern of pluripotent cells reflects...
Article
Full-text available
The controlled and stepwise oxidation of 5mC to 5hmC, 5fC and 5caC by Tet enzymes is influencing the chemical and biological properties of cytosine. Besides direct effects on gene regulation, oxidised forms influence the dynamics of demethylation and re-methylation processes. So far, no combined methods exist which allow to precisely determine the...
Article
Full-text available
Regulatory T cells (Tregs) are an attractive therapeutic tool for several different immune pathologies. Therapeutic Treg application often requires prolonged in vitro culture to generate sufficient Treg numbers or to optimize their functionality, e.g., via genetic engineering of their antigen receptors. However, purity of clinical Treg expansion cu...
Chapter
The accurate and quantitative detection of 5-methylcytosine is of great importance in the field of epigenetics. The method of choice is usually bisulfite sequencing because of the high resolution and the possibility to combine it with next generation sequencing. Nevertheless, also this method has its limitations. Following the bisulfite treatment D...
Conference Paper
DNA methylation is an epigenetic mechanism whose important role in development has been widely recognized. This epigenetic modification results in heritable changes in gene expression not encoded by the DNA sequence. The underlying mechanisms controlling DNA methylation are only partly understood and recently different mechanistic models of enzyme...
Preprint
Full-text available
DNA methylation is an epigenetic mechanism whose important role in development has been widely recognized. This epigenetic modification results in heritable changes in gene expression not encoded by the DNA sequence. The underlying mechanisms controlling DNA methylation are only partly understood and recently different mechanistic models of enzyme...
Article
Full-text available
Background In the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The parental genomes of the zygote show distinct patterns of histone H3 variants and distinct patterns of DNA and histone modifications. The molecular mechanisms linking histone variant-specific m...
Article
Full-text available
Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further characterize the dynamics and consequenc...
Article
Full-text available
Motivation: Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at Cp...
Article
Full-text available
DNA methylation and demethylation are opposing processes that when in balance create stable patterns of epigenetic memory. The control of DNA methylation pattern formation by replication dependent and independent demethylation processes has been suggested to be influenced by Tet mediated oxidation of 5mC. Several alternative mechanisms have been pr...
Data
Details on the theoretical model, the parameter estimation, the statistical analysis of the results and the experimental procedure. (PDF)
Data
Comparison of model prediction and data for IAP, L1mdA, MuERVL, Ttc25 and Snrpn. Plotted according to Fig 5. (PDF)
Data
(Hydroxy-)methylation levels for each single CpG dyad of repetitive elements IAP, L1mdA, L1mdT, mSat, MuERVL and single copy genes Afp, Ttc25, Zim3 and Snrpn over time. The colormap is the same as in Fig 6. (PDF)
Data
Estimated coefficients of the functions μd(t), μm(t) and η(t) and their approximate standard deviations. The p-values have been taken conducting a hypothesis test H0: β1 = 0 using the Wald statistic. (PDF)
Data
BS and oxBS data, Conversion Errors (repetitive elements). (PDF)
Data
Results for loci IAP, L1mdA, MuERVL, Ttc25 and Snrpn. Left: Probabilities of the hidden states. Plotted according to Fig 6. Right: Estimated efficiencies and standard deviations over time. Plotted according to Fig 7 (PDF)
Data
Estimated efficiencies and standard deviations for each single CpG dyad of repetitive elements IAP, L1mdA, L1mdT, mSat, MuERVL and single copy genes Afp, Ttc25, Zim3 and Snrpn over time. In the case of IAP we cover six CpG positions. However, during evolution CpG one and five underwent a transition resulting in a loss of the CpG positions in this p...
Data
BS and oxBS data, Conversion Errors (single copy genes). (PDF)
Data
Test error: Linear vs Constant Assumption. Computed Kullback-Leibler divergence and Bhattacharya distance values given by LOOCV data to compare the test error for assuming linear vs constant efficiencies. (PDF)
Data
Bs and oxBS data for single CpGs. The dataset contains the BS and oxBS data of each single CpG and loci after processing of the sequencing data; error rates are included as separate files. Raw sequencing data are available on request. (ZIP)
Data
Estimated coefficients of the function λ(t) and their approximate standard deviations. The p-values have been taken conducting a hypothesis test H0:β1λ=0∧β2λ=0 using the Wald statistic. (PDF)
Article
Stable expression of Foxp3 in regulatory T cells (Tregs) depends on DNA demethylation at the Treg-specific demethylated region (TSDR), a conserved, CpG-rich region within the Foxp3 locus. The TSDR is selectively demethylated in ex vivo Tregs purified from secondary lymphoid organs, but it is unclear at which stage of Treg development demethylation...

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