Biology subjects

Klenova, E.

Publications and source records attributed to Klenova, E..

2 recordsLinked to original sources

bioRxiv2017

Activation of the Androgen Receptor gene by BORIS/CTCFL in prostate cancer cells

BORIS/CTCFL, a paralogue of the chromatin architectural protein CTCF, is a member of the cancer-testis antigen family, normally present in the testes. BORIS is expressed in various tumours, including prostate cancers, however the function of BORIS in cancer cells is not well defined. The androgen receptor (AR) plays a critical role in the normal development of a human prostate gland and pathogenesis of prostate cancer. In our previous study we described a positive correlation between elevated levels of BORIS and AR in prostate cancers, and activation of the AR gene by BORIS in prostate cancer cells. Elucidation of the mechanisms involved in the modulation of AR activity is important to understand prostate tumourigenesis and investigation of transcriptional regulation of the AR gene by BORIS may provide new insights into this issue. Here we report the ability of BORIS to not only positively regulate AR in androgen-dependent prostate cancer (ADPC) cells, but re-activate epigenetically silenced AR in androgen-independent prostate cancer (AIPC) cells leading to the production of biologically active AR protein. CTCF, on the other hand, had repressive effects on the AR. In both, ADPC and AIPC cells, introduction of ectopic BORIS was associated with the reduction in the AR promoter methylation, increase in active and decrease in repressive chromatin marks, and decrease in CTCF occupancies at the two main upstream BORIS/CTCF binding sites. We propose a model of epigenetic regulation of AR by BORIS in prostate cells whereby BORIS remodels the chromatin at the AR promoter leading to transcriptional activation.

cancer biology↗

bioRxiv2017

Poly(ADP-ribosyl)ation dependent changes in CTCF-chromatin binding and gene expression in breast cells

CTCF is an evolutionarily conserved and ubiquitously expressed architectural protein regulating a plethora of cellular functions via different molecular mechanisms. CTCF can undergo a number of post-translational modifications which change its properties and functions. One such modifications linked to cancer is poly(ADP-ribosyl)ation (PARylation). The highly PARylated CTCF form has an apparent molecular mass of 180 kDa (referred to as CTCF180), which can be distinguished from hypo- and non-PARylated CTCF with the apparent molecular mass of 130 kDa (referred to as CTCF130). The existing data accumulated so far have been mainly related to CTCF130. However, the properties of CTCF180 are not well understood despite its abundance in a number of primary tissues. In this study we performed ChIP-seq and RNA-seq analyses in human breast cells 226LDM, which display predominantly CTCF130 when proliferating, but CTCF180 upon cell cycle arrest. We observed that in the arrested cells the majority of sites lost CTCF, whereas fewer sites gained CTCF or remain bound (i.e. common sites). The classical CTCF binding motif was found in the lost and common, but not in the gained sites. The changes in CTCF occupancies in the lost and common sites were associated with increased chromatin densities and altered expression from the neighboring genes. Based on these results we propose a model integrating the CTCF130/180 transition with CTCF-DNA binding and gene expression changes. This study also issues an important cautionary note concerning the design and interpretation of any experiments using cells and tissues where CTCF180 may be present.

molecular biology↗