Research output: Contribution to journal › Article › peer-review
The 3D genomics of lampbrush chromosomes highlights the role of active transcription in chromatin organization. / Lagunov, Timofey; Gridina, Maria; Nurislamov, Artem; Kulikova, Tatiana; Maslova, Antonina; Konstantinov, Viktor; Popov, Andrey; Krasikova, Alla; Fishman, Veniamin.
In: Nucleic Acids Research, Vol. 54, No. 7, gkag316, 28.03.2026.Research output: Contribution to journal › Article › peer-review
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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 - © The Author(s) 2026. Published by Oxford University Press.
PY - 2026/3/28
Y1 - 2026/3/28
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.
KW - Chromatin/genetics
KW - Transcription, Genetic
KW - Animals
KW - Genomics/methods
KW - Chromosomes/genetics
KW - Mice
KW - Meiosis/genetics
KW - Oogenesis/genetics
KW - Single-Cell Analysis
UR - https://www.mendeley.com/catalogue/3a277157-ef9e-34ce-b5dd-fa441b682298/
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 -
ID: 152363372