Research Laboratory «‎Regulatory Genomics»

Hayashizaki Yoshihide

Contract number

075-15-2021-601

Time span of the project

2021-2023

Laboratory's website

As of 01.12.2023

Number of staff members

scientific publications

Name of the project: Regulatory genetic and epigenetic mechanisms of the development and the functioning of skeletal muscles and the heart muscle of humans and primates in the norm and pathology

Goals of project:

The main objective of this research is the determination of the activity landscape of regulatory elements of the genome in the adult and developing heart muscles of humans and primates in the norm and pathology. To achieve this goal, it will be necessary to collect samples of various types of skeletal and heart muscles of humans and mammals (macaques). The organisation of a biological bank of muscle samples will be one of the important tasks. Using modern methods of the assessment of the activity of genes at the level of the whole genome (CAGE-seq RNA-seq) and their regulatory elements (ATAC-seq), as well as their variations at the level of single cells, we will be solving the problem of the collection of an array of sequencing data. The obtained data will be processed by a group of bioinformaticians possessing the experience of completion of major international projects, as well as using the FANTOM project series (2000-2018) that was based on the same technological platform (CAGE-seq), for the comparison of the results.

As a result, we are planning to create an atlas of expression activity, a reconstruction of gene networks that regulate molecular processes in muscle cells and tissues in the norm and pathology.

Scientific results:

In the framework of the preparation of the pilot project for the launch of the scientific and clinical muscle biobank, the analysis of genes active in skeletal and cardiac muscles and, at the same time, associated with the development of myopathies was continued. With the advisory support of the Bochkov Medical Genetics Research Center, the expression of such genes was assessed in the FANTOMUS skeletal muscle expression atlas created by us and patterns of the relationship between the expression of such genes and the resistance of skeletal muscles to dystrophy were identified. In partnership with the IBMB RAS, using the FANTOMUS atlas as a reference, an analysis of transcriptional changes in human muscles under the influence of artificial microgravity (using dry immersion) was carried out. For the first time, key transcription factors associated with signaling molecular pathways responding to gravitational unloading were identified. An article has been prepared for the journal Q1.

A comprehensive analysis of the genes encoding myosins and the regulatory regions of such genes is being carried out. Expression of “embryonic” myosins in a number of adult human skeletal muscles is shown. An analysis of myosin isoforms transcribed from various promoters is conducted. A new algorithm for direct comparison of regulatory regions of the human and macaque genomes is developed. This approach will be used at the next stage of the analysis – characterization of evolutionary changes in regulatory regions of the genome and related functional features of orthologous muscles of humans and primates.

Implementation of research results:

Based on the results of the project implementation, a roadmap has been prepared for the implementation of bioinformatic analysis of regulatory elements of the human genome active in muscles in the program of genetic diagnostics of myopathies of unclear origin. The concept of the muscle scientific and clinical biobank project (with the involvement of transcription analysis) is being developed.

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Penzar D, Nogina D, Noskova E, Zinkevich A, Meshcheryakov G, Lando A, Rafi AM, de Boer C, Kulakovskiy IV.

LegNet: a best-in-class deep learning model for short DNA regulatory regions. Bioinformatics. 2023 Aug 1;39(8):btad457. doi:10.1093/bioinformatics/btad457

Penzar D, Nogina D, Noskova E, Zinkevich A, Meshcheryakov G, Lando A, Rafi AM, de Boer C, Kulakovskiy IV.

An atlas of transcribed human cardiac promoters and enhancers reveals an important role of regulatory elements in heart failure. Nat Cardiovasc Res 2, 58–75 (2023). https://doi.org/10.1038/s44161-022-00182-x

Vorontsov IE, Eliseeva IA, Zinkevich A, Nikonov M, Abramov S, Boytsov A, Kamenets V, Kasianova A, Kolmykov S, Yevshin IS, Favorov A, Medvedeva YA, Jolma A, Kolpakov F, Makeev VJ, Kulakovskiy IV

HOCOMOCO in 2024: a rebuild of the curated collection of binding models for human and mouse transcription factors. Nucleic Acids Res. 2024 Jan 5;52(D1):D154-D163. doi: 10.1093/nar/gkad1077

Aitova A, Berezhnoy A, Tsvelaya V, Gusev O, Lyundup A, Efimov AE, Agapov I, Agladze K.

Biomimetic Cardiac Tissue Models for In Vitro Arrhythmia Studies. Biomimetics (Basel). 2023 Oct 14;8(6):487. doi: 10.3390/biomimetics8060487.

Hosting organization	Field of studies	City	Invited researcher	Time span of the project
Centre for Integrative Structural Biology (10) National Research Centre «Kurchatov Institute» - (Kurchatov Institute)	Biology	Moscow	Yusupov Marat Russia, France	2024-2028
Laboratory of Revolutionary Trophology A.N. Severtsov Institute of Ecology and Evolution of RAS - (IEE RAS)	Biology	Moscow	Gisbert Enric Casas Spain	2022-2024
Laboratory for Statistical Multi-omics and Bio-informatics Ufa Federal Research Centre of the Russian Academy of Sciences	Biology	Ufa	Prokopenko Inga Anatoliyevna United Kingdom	2021-2023