Biopolym. Cell. 2019; 35(3):193-194.
Chronicle and Information
The systematic study on the epigenomics of mei-Cohesins in the norm and as Cancer-Testis proteins
1Boukaba A., 1Wu Q., 1Liang J., 1Liu J., 3Pugacheva E. M., 3Lobanenkov V., 1, 2Strunnikov A.
  1. Molecular Epigenetics Laboratory, Guangzhou Institutes of Biomedicine and Health, Guangzhou
    Guangdong, China
  2. The University of the Chinese Academy of Sciences
    Beijing, China
  3. Laboratory of Immunogenetics, NIH, NIAID
    Rockville, MD, USA

Abstract

Meiotic cohesin subunits are frequently expressed in cancers as Cancer-Testis (CT) Genes, and are potentially linked to the onset and proliferation of tumor cells. However, the roles of CT genes, and mei-Cohesin components in particular, in cancer were not studied in depth. In order to address this gap in research we took two approaches : the epigenomics of mei-Cohesin in normal primate testis and the reconstitution of mei-Cohesin complexes in somatic cell lines, both normal and transformed. Applying a novel ChIP-ChEP-seq method in Macaca fascicularis testis, we elucidated the overlapping pattern of mei-Cohesin binding to germline chromosome arms and centromeric repeats for SMC1b, STAG3, RAD21L and REC8 subunits. We also uncovered the rules guiding the cohabitation of mei-Cohesins with BORIS/CTCFL and CTCF-containing regulatory sites controlling gene expression and 3D chromatin structure during the spermatogenesis. Finally, by reconstituting REC8 and RAD21L based mei-Cohesin complexes in human somatic cell lines, we discovered the governing principles for mei-Cohesin binding to chromatin. The introduction of particular combinations of mei-Cohesin subunits into such a system was setting up a potential competition with somatic cohesin complex based on RAD21, resulting in chromosome instability phenotype. As a result of this work, we elucidated the potential biological roles of mei-Cohesin expressed as CT genes in cancer cells.