“Shaping Chromatin Structure in Development and Transcriptional Regulation”, Aleksandra Pekowska, Nencki Institute of Experimental Biology PAS, Poland

Speaker: Aleksandra Pekowska, Polish Academy of Sciences, Poland

Host: Michal Slezak, BioMed X

Abstract

“Topologically Associating Domains (TADs) are megabase-sized genomic intervals of preferential genomic contacts. TADs provide the framework for understanding the functional interplay between cis-regulatory elements. The formation of TADs critically relies on the concert action of cohesins and CTCF, an eleven zinc finger insulator protein. Cohesins tether sequences to each other while CTCF underlies the formation of TAD boundaries by limiting the interactions to regions within TADs. The two CTCF-enriched TAD boundaries frequently form a strong interaction reminiscent of a loop.

I will show our previous and current work where we combined high-throughput sequencing approaches, including in-situ HiC, and computational tools to address the question of how cohesins and CTCF participate in the regulation of genome topology and in the control of gene expression. I will present data connecting cellular energy consumption and cohesin action on chromatin. I will introduce architectural stripes, a specialized chromatin structure formed by super-enhancers, that intervenes in the regulation of promoter activity. In the second part of the talk, I will show the timing of the maturation of chromatin structure during the earliest stages of mammalian development.”

About Aleksandra

“I graduated from the University of Lodz (specialization: biophysics) in 2006. For my Ph.D., I joined Dr. Pierre Ferrier’s lab at the CIML in Marseilles. I probed the activity of genes and enhancers in various cellular contexts, including developing T cells and in leukemia patient cells. I applied a variety of high throughput genome analysis technologies (ChIP-seq, RNA-seq, and microarray-based approaches) and computational biology tools. We discovered a chromatin signature allowing us to distinguish active from poised enhancers (Pękowska A. et al., 2011, EMBO J). In a purely in silico study, we show for the first time, that tissue-specific genes display a unique pattern of histone modifications (Pękowska A. et al., 2010 Genome Res.). In 2011, I obtained the EIPOD fellowship (EMBL/Marie Curie actions). I joined groups of Dr. Wolfgang Huber, Dr. Lars Steinmetz at EMBL, and the lab of Dr. Paul Bertone and EBI. I investigated the relationship between cellular plasticity and chromatin topology. Using Hi-C, we found that the differentiation of pluripotent stem cells to neuronal lineage coincides with a genome-wide buildup of chromatin loops (Pekowska et al., 2018 Cell Sys.). In 2016, I joined the team of Dr. Rafael Casellas at NIAMS (NIH). In a recent paper, we described architectural stripes – specialized chromatin structures frequently involving super-enhancers (Vian L.#, Pękowska A.# et al. 2018 Cell). Combining CRISPR-Cas9, Hi-C, and ChIP-seq, we show that stripes critically rely on the action of CTCF and cohesins; and that their formation requires constant energy input. Recently (October 2019), I opened my lab – Dioscuri Center of Chromatin Biology and Epigenomics at the Nencki Institute of Experimental Biology in Warsaw. In our work, we combine ‘omics’ approaches, CRISPR-Cas9, and stem cell tools. The far-reaching goal of our research is, on the one hand, to understand the implication of genome topology in the regulation of gene expression. On the other hand, we aim to provide new insights into the genetic bases of human brain evolution.”