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Active chromatin regions are sufficient to define borders of topologically associated domains in D. melanogaster interphase chromosomes Ekaterina E. Khrameeva
Skolkovo Institute of Science and Technology, Novaya st. 100, Skolkovo 143025, Russia, Institute for Information Transmission Problems, RAS, Bolshoy Karetny per. 19/1, Moscow 127051, Russia e.khrameeva@skoltech.ru

Sergey V. Ulyanov, Alexey A. Gavrilov
Institute of Gene Biology, RAS, Vavilova st. 34/5, Moscow 119334, Russia

Yuri Y. Shevelyov
Institute of Molecular Genetics, RAS, Akademika Kurchatova pl. 2, Moscow 123182, Russia

Sergey V. Razin
Institute of Gene Biology, RAS, Vavilova st. 34/5, Moscow 119334, Russia sergey.v.razin@usa.net

In Drosophila, interphase chromosomes are organized in topologically associated domains (TADs) within which chromatin-chromatin interactions are frequent, while interactions across domain borders are rare [1]. TAD positions on chromosomes appear to be conservative between cells of different lineages, and even between animal species [2]. However, molecular mechanisms underlying partitioning of chromosomes in TADs are poorly understood. Insulator elements have been proposed [1-3] to play a key role in definition of TAD borders but recently experimental evidences against this hypothesis have appeared [4]. Here we used Hi-C method [5] to map TADs in four drosophila cell lines of different origin. The cell lines share up to 80% TAD positions, while cell type specific TAD borders correlate with transcription changes between cell lines. TADs appear to be self-organizing condensed chromatin domains depleted in active chromatin marks (Fig. 1A). Active chromatin regions that cannot be organized in compact structures separate TADs, being sufficient to establish TAD borders without contribution of insulator proteins, such as Su(Hw) or CTCF (Fig. 1B).

Fig. 1. Distribution of active chromatin marks and insulator protein sites in 20 kb bins surrounding aligned TAD boundaries. A. Proportion of chromatin colors in TADs and inter-TADs calculated as an average proportion of chromatin colors (as annotated in [6]) in aligned bins. B. Enrichment of chromatin marks and insulator protein binding sites in TADs and inter-TADs. The enrichment was calculated as the median proportion of ChIP-seq peaks (provided in modENCODE database [7]) in aligned bins, multiplied by the peak scores, and Z-transformed to make different chromatin features comparable. Blue lines correspond to Kc167 cells, green lines to ML-DmBG3 cells, and red lines to S2-DRSC cells.

This work was supported by RFBR grant number 13-04-40089. This is joint work with Mikhail S. Gelfand, Institute for Information Transmission Problems, RAS.

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