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Kesseli, J.

Publications and source records attributed to Kesseli, J..

2 recordsLinked to original sources

The transcription factor network of E. coli steers global responses to shifts in RNAP concentration

The robustness and sensitivity of gene networks to environmental changes is critical for cell survival. How gene networks produce specific, chronologically ordered responses to genome-wide perturbations, while robustly maintaining homeostasis, remains an open question. We analysed if short- and mid-term genome-wide responses to shifts in RNA polymerase (RNAP) concentration are influenced by the known topology and logic of the transcription factor network (TFN) of Escherichia coli. We found that, at the gene cohort level, the magnitude of the single-gene, mid-term transcriptional responses to changes in RNAP concentration can be explained by the absolute difference between the genes numbers of activating and repressing input transcription factors (TFs). Interestingly, this difference is strongly positively correlated with the number of input TFs of the gene. Meanwhile, short-term responses showed only weak influence from the TFN. Our results suggest that the global topological traits of the TFN of E. coli shape which gene cohorts respond to genome-wide stresses.

systems biology↗

Chromatin accessibility analysis uncovers regulatory element landscape in prostate cancer progression

Aberrant oncogene functions and structural variation alter the chromatin structure in cancer cells. While gene regulation by chromatin states has been studied extensively, chromatin accessibility and its relevance in aberrant gene expression during prostate cancer progression is not well understood. Here, we report a genome-wide chromatin accessibility analysis of clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration-resistant prostate cancer (CRPC) and integrative analysis with transcriptome, methylome, and proteome profiles of the same samples to uncover disease-relevant regulatory elements and their association to altered gene expression during prostate cancer progression. While promoter accessibility is consistent during disease initiation and progression, at distal sites chromatin accessibility is variable enabling transcription factors (TFs) binding patterns that are differently activated in different patients and disease stages. We identify consistent progression-related chromatin alterations during the progression to CRPC. By studying the TF binding patterns, we demonstrate the activation and suppression of androgen receptor-driven regulatory programs during PC progression and identify complementary TF regulatory modules characterized by e.g. MYC and glucocorticoid receptor. By correlation analysis we assign at least one putative regulatory region for 62% of genes and 85% of proteins differentially expressed during prostate cancer progression. Taken together, our analysis of the chromatin landscape in PC identifies putative regulatory elements for the majority of cancer-associated genes and characterizes their impact on the cancer phenotype.

cancer biology↗