TY - JOUR

T1 - The 3D genomics of lampbrush chromosomes highlights the role of active transcription in chromatin organization

AU - Lagunov, Timofey

AU - Gridina, Maria

AU - Nurislamov, Artem

AU - Kulikova, Tatiana

AU - Maslova, Antonina

AU - Konstantinov, Viktor

AU - Popov, Andrey

AU - Krasikova, Alla

AU - Fishman, Veniamin

N1 - Timofey Lagunov, Maria Gridina, Artem Nurislamov, Tatiana Kulikova, Antonina Maslova, Viktor Konstantinov, Andrey Popov, Alla Krasikova, Veniamin Fishman, The 3D genomics of lampbrush chromosomes highlights the role of active transcription in chromatin organization, Nucleic Acids Research, Volume 54, Issue 7, 24 April 2026, gkag316, https://doi.org/10.1093/nar/gkag316 This study was initiated with support of RSF Project # 20-64-46021 in 2020-2022 (most of the genomic and cytological experiments). Access to computational resources was provided by Novosibirsk State University, supported by the Ministry of Education and Science of the Russian Federation (FSUS-2024-0018). Part of the bioinformatic analysis (including LBC 3Dmodelling and genome annotation) and manuscript preparation was supported by grant of the state program of the “Sirius” Federal Territory “Scientific and technological development of the “Sirius” Federal Territory” (agreement # 26-03, 27/09/2024).

PY - 2026/4/24

Y1 - 2026/4/24

N2 - Lampbrush chromosomes (LBCs) are giant meiotic bivalents that have served as a classic model system for studying chromatin organization and RNA synthesis for over a century. Despite their importance, the molecular mechanisms underlying distinctive LBC chromomere–loop architecture have remained poorly understood. Moreover, the influence of hypertranscription on chromatin organization during oogenesis remains enigmatic. Here, we provide comprehensive analysis of LBC organization by integrating single-cell Hi-C, RNA-seq, NOMe-seq, FISH mapping, and chromatin simulations. Single-nucleus Hi-C revealed CTCF-independent contact domains with stable boundaries defined by convergently oriented transcription units (TUs). Contact domains identified through Hi-C analysis correspond to insulated chromomeres in LBCs. Small transcriptionally inactive contact domains surrounded by divergently oriented TUs form “chromatin knots,” which are often detached from the chromosome axis. Transcription loops frequently manifest as a “cross” pattern with reduced contacts within chromatin domains. Integrative analysis of the whole-genome data uncovers the mechanisms underlying LBC structure, revealing how hypertranscription modulates chromatin stiffness and repositions SMC complexes to establish the distinctive chromomere–loop organization. Biophysical modeling through polymer simulation reproduces key features of LBCs, including transcription loop formation, chromomere compaction, and insulation patterns. These findings offer a unifying framework for understanding remarkable transcription-dependent organization of LBCs.

AB - Lampbrush chromosomes (LBCs) are giant meiotic bivalents that have served as a classic model system for studying chromatin organization and RNA synthesis for over a century. Despite their importance, the molecular mechanisms underlying distinctive LBC chromomere–loop architecture have remained poorly understood. Moreover, the influence of hypertranscription on chromatin organization during oogenesis remains enigmatic. Here, we provide comprehensive analysis of LBC organization by integrating single-cell Hi-C, RNA-seq, NOMe-seq, FISH mapping, and chromatin simulations. Single-nucleus Hi-C revealed CTCF-independent contact domains with stable boundaries defined by convergently oriented transcription units (TUs). Contact domains identified through Hi-C analysis correspond to insulated chromomeres in LBCs. Small transcriptionally inactive contact domains surrounded by divergently oriented TUs form “chromatin knots,” which are often detached from the chromosome axis. Transcription loops frequently manifest as a “cross” pattern with reduced contacts within chromatin domains. Integrative analysis of the whole-genome data uncovers the mechanisms underlying LBC structure, revealing how hypertranscription modulates chromatin stiffness and repositions SMC complexes to establish the distinctive chromomere–loop organization. Biophysical modeling through polymer simulation reproduces key features of LBCs, including transcription loop formation, chromomere compaction, and insulation patterns. These findings offer a unifying framework for understanding remarkable transcription-dependent organization of LBCs.

UR - https://www.mendeley.com/catalogue/3a277157-ef9e-34ce-b5dd-fa441b682298/

UR - https://www.scopus.com/pages/publications/105035679424

U2 - 10.1093/nar/gkag316

DO - 10.1093/nar/gkag316

M3 - Article

C2 - 41978268

VL - 54

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 7

M1 - gkag316

ER -