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Representation of intracellular signaling networks as directed graphs allows for the identification of regulatory motifs. Regulatory motifs are groups of nodes with the same connectivity structure, capable of processing information. The…
To regulate a particular gene, a transcription factor (TF) needs to bind a specific genome location. How is this genome address specified amid the presence of ~10^6-10^9 decoy sites? Our analysis of 319 known TF binding motifs clearly…
Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect…
Experimental evidence suggests that epidermal growth factor receptor (EGFR)-mediated activation of the signaling protein phospholipase C gamma plays a critical role in a cancer cell's phenotypic decision to either proliferate or to migrate…
The activities and interactions of proteins that govern the cellular response to a signal generate a multitude of protein phosphorylation states and heterogeneous protein complexes. Here, using a computational model that accounts for 307…
Central to the functioning of a living cell is its ability to control the readout or expression of information encoded in the genome. In many cases, a single transcription factor protein activates or represses the expression of many genes.…
In addition to their self-renewal capabilities, hematopoietic stem cells guarantee the continuous supply of fully differentiated, functional cells of various types in the peripheral blood. The process which controls differentiation into the…
Reproduction and natural selection are the key elements of life. In order to reproduce, the genetic material must be doubled, separated and placed into two new daughter cells, each containing a complete set of chromosomes and organelles. In…
Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key…
The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic…
Somatic mutations in cancer cells affect various genomic elements disrupting important cell functions. In particular, mutations in DNA binding sites recognized by transcription factors can alter regulator binding affinities and expression…
Recurrence and metastasis have been regarded as two of the greatest obstacles for curing cancer. Cancer stem cell (CSC) have been found. They contribute to cancer development with the distinct feature of recurrence and resistance to the…
The emergence of and transitions between distinct phenotypes in isogenic cells can be attributed to the intricate interplay of epigenetic marks, external signals, and gene regulatory elements. These elements include chromatin remodelers,…
Transcriptional and post-transcriptional regulation shape tissue-type-specific proteomes, but their relative contributions remain contested. Estimates of the factors determining protein levels in human tissues do not distinguish between (i)…
The mitogen activated protein kinase (MAPK) family of proteins is involved in regulating cellular fate activities such as proliferation, differentiation and apoptosis. Their fundamental importance has attracted considerable attention on…
It is well known that cyclins are a family of proteins that control cell-cycle progression by activating cyclin-dependent kinase. Based on our experimental results, we propose here a novel hypothesis that certain amplified genomic-DNA…
The research reported in this paper identifies the epigenetic biomarker (methylation beta pattern) of breast cancer. Many cancers are triggered by abnormal gene expression levels caused by aberrant methylation of CpG sites in the DNA. In…
Genetic variation affecting gene regulation is a central driver of phenotypic differences between individuals and can be used to uncover how biological processes are organized in a cell. Although detecting cis-eQTLs is now routine,…
Antiterminators are essential components of bacterial transcriptional regulation, allowing the control of gene expression in response to fluctuating environmental conditions. Among them, RNA-binding antiterminator proteins play a major role…
Molecular chaperones play a prominent role in signaling and transcriptional regulatory networks of the cell. Recent advances uncovered that chaperones act as genetic buffers stabilizing the phenotype of various cells and organisms and may…