Cohesin in chromatin structure and gene regulation
Our genome contains in total 3.2 x 10 9 nucleotide pairs which give a DNA helix of around 2 m when stretched out. To fit this strand in the tiny volume of a cell nucleus the strand is tightly packed by histones and other proteins.
Cohesin and its family member condensin are crucial for organizing this chromatin fibre during processes which require reorganization of the fibre. During cell division the whole genome is duplicated and equally distributed onto daughter cells. Cohesin is a major factor to ensure that the genome stably inherited. It enables the cells to properly identify the identical copies of the genome by tethering both copies tightly together.
Recent research has identified more than 30.000 binding sites of cohesin in the human genome and the complex was also shown to have important role for controlling gene activity in interphase in several organisms.
We propose that cohesin might control gene activity by a similar mechanism as it organizes DNA strands during cell division. Distant DNA elements might be hold together by cohesin, resulting in the formation of large chromatin loops which interfere with promoter-enhancer communication, resulting in altered gene activity. We have discovered such cohesin-dependent loops at the human H9/IGF2 locus.
We are studying whether cohesin-dependent chromatin structures are a major gene regulatory mechanism in the human genome and use chromatin conformation capturing and genomic sequencing to study the chromosomal contacts of cohesin binding sites.
Furthermore, we are interested in the molecular mechanism how cohesin establishes these intra-strand chromatin interactions. Therefore we are studying known cohesin regulators such as CTCF and NIPBL for their role in higher order chromatin structures. In addition we identify novel factors which have not been linked to cohesin function yet, but might have important roles in the molecular mechanism.
