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High-resolution chromatin mapping reveals that CTCF in anchors meiotic loops to the chromosome axis. [microC]

ABSTRACT: When precursor germ cells enter meiosis, chromosomes condense into an array of chromatin loops. Using Hi-C and Micro-C, we explored the trajectory of chromatin reorganization from mouse spermatogonia to spermatocytes at the highest temporal and spatial resolution to date. We show that meiotic chromatin reorganization, characterized by a shift from mitotic-to-meiotic cohesins, precedes the traditionally defined meiotic entry point (meiotic G1/S-phase). We find that large-scale A/B compartments are lost during prophase I, while local sub-compartments and interactions between regulatory elements of gene expression remain. For the first time, we detect distinct looping positions in mammalian meiosis I prophase. These loops are anchored by a subset of CTCF sites at the base of chromatin loops but formed without enriched interactions within the intervening regions, deviating from the typical pattern observed in somatic interphase cells. Our findings allow us to reconcile the current discrepancy in the length of meiotic chromatin loops and support a model where meiotic loops are formed by association of existing loops modulated by CTCF rather than by loop extrusion.

ORGANISM(S): Mus musculus

PROVIDER: GSE288839 | GEO | 2026/02/26

REPOSITORIES: GEO

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High-resolution chromatin mapping reveals that CTCF in anchors meiotic loops to the chromosome axis. [Hi-C]

Project description:When precursor germ cells enter meiosis, chromosomes condense into an array of chromatin loops. Using Hi-C and Micro-C, we explored the trajectory of chromatin reorganization from mouse spermatogonia to spermatocytes at the highest temporal and spatial resolution to date. We show that meiotic chromatin reorganization, characterized by a shift from mitotic-to-meiotic cohesins, precedes the traditionally defined meiotic entry point (meiotic G1/S-phase). We find that large-scale A/B compartments are lost during prophase I, while local sub-compartments and interactions between regulatory elements of gene expression remain. For the first time, we detect distinct looping positions in mammalian meiosis I prophase. These loops are anchored by a subset of CTCF sites at the base of chromatin loops but formed without enriched interactions within the intervening regions, deviating from the typical pattern observed in somatic interphase cells. Our findings allow us to reconcile the current discrepancy in the length of meiotic chromatin loops and support a model where meiotic loops are formed by association of existing loops modulated by CTCF rather than by loop extrusion.

2026-02-26 | GSE288838 | GEO

High-resolution chromatin mapping reveals that CTCF in anchors meiotic loops to the chromosome axis.

2026-02-26 | GSE288837 | GEO

Reorganized 3D genome structures support transcriptional regulation in mouse spermatogenesis

Project description:Three-dimensional chromatin structures undergo dynamic reorganization during mammalian spermatogenesis; however, their impacts on gene regulation remain unclear. Here, we focused on understanding the structure-function regulation of meiotic chromosomes by Hi-C and other omics techniques in mouse spermatogenesis across five sequential stages. Beyond confirming recent reports regarding changes in compartmentalization and reorganization of topologically associating domains (TADs), we further demonstrated that chromatin loops are present prior to and after, but not at, the pachytene stage. By integrating Hi-C and RNA-Seq data, we showed that the switching of A/B compartments between spermatogenic stages is tightly associated with meiosis-specific mRNAs and piRNAs expression. Moreover, our ATAC-Seq data indicated that chromatin accessibility per se is not responsible for the TAD and loop diminishment at pachytene. Additionally, our ChIP-Seq data demonstrated that CTCF and cohesin remain bound at TAD boundary regions throughout meiosis, suggesting that dynamic reorganization of TADs does not require CTCF and cohesin clearance.

2020-03-26 | GSE147536 | GEO

Chromatin remodeler CHD8 is required for spermatogonial proliferation and early meiotic progression

Project description:Meiosis is a key step during germ cell differentiation, accompanied by the activation of thousands of genes through germline-specific chromatin reorganization. The chromatin remodeling mechanisms underpinning early meiotic stages remain poorly understood. Here we focus on the function of one of the major autism genes, CHD8, in spermatogenesis, based on the epidemiological association between autism and low fertility rates. Specific ablation of Chd8 in germ cells results in gradual depletion of undifferentiated spermatogonia as well as failure of meiotic double strand formation followed by arrest at meiotic prophase I and cell death. Transcriptional analyses demonstrate that CHD8 is required for extensive activation of spermatogenic genes in spermatogonia, necessary for spermatogonial proliferation and meiosis. CHD8 directly binds to promoters of genes crucial for meiosis, including H3K4me3 histone methyltransferase genes, meiotic cohesin genes, HORMA domain containing genes, synaptonemal complex genes, and DNA damage response genes. Through transcriptionally regulating the interaction of these meiosis-related genes, we argue that CHD8 contributes to meiotic double strand break formation and subsequent meiotic progression. Our study uncovers an essential role of CHD8 for the proliferation of undifferentiated spermatogonia and the successful progression of meiotic prophase I.

2023-12-31 | GSE252121 | GEO

Dynamic Reorganization of the Genome Shapes the Recombination Landscape in Meiotic Prophase

Project description:In meiotic prophase, chromosomes are organized into compacted loop arrays to promote homolog pairing and recombination. Here, we probe the architecture of the mouse spermatocyte genome in early and late meiotic prophase using Hi-C. We show that early-prophase chromosomes are arranged as linear arrays of 0.8-1 Mb loops, which extend to 1.5-2 Mb in late prophase as chromosomes compact and homologs undergo synapsis. Topologically associating domains (TADs) are lost in meiotic prophase, suggesting that assembly of the meiotic chromosome axis dramatically reduces the dynamics of chromosome-associated cohesin complexes. While TADs are lost, physically-separated A and B compartments are maintained in meiotic prophase. Moreover, meiotic DNA breaks and inter-homolog crossovers preferentially form in the gene-dense A compartment, revealing a role for chromatin organization in meiotic recombination. Finally, direct detection of inter-homolog contacts genome-wide reveals the structural basis for homolog alignment and juxtaposition by the synaptonemal complex.

2018-11-17 | GSE122622 | GEO

Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at the promoters of genes expressed during meiosis [CUT&RUN]

Project description:Meiotic prophase I characterized by homologous recombination and synapsis is an intricate step for spermatogenesis. This process entails extensive changes to chromatin and transcription. Recent studies have revealed that prior to prophase I, accessible chromatin bound by paused Pol II at meiotic gene promoters is essential for their timely activation during later stages of prophase I. However, the factor responsible for promoting accessible chromatin at meiotic gene promoters before entry into prophase I is unknown. Here, we discovered that NFYA expressed in pre-meiotic germ cells promotes accessible chromatin at meiotic gene promoters. Concordantly, conditional germline deletion of Nfya in male mice blocks meiotic entry. Functionally, our spatial and single-cell ATAC-seq data revealed that loss of NFYA in pre-meiotic cells disrupts accessible chromatin at meiotic gene promoters. Our study identifies a pioneer role for NFYA in facilitating permissive chromatin at meiotic gene promoters before meiosis, thereby controlling the timely activation of meiotic genetic program during later meiosis.

2025-05-10 | GSE295964 | GEO

Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at the promoters of genes expressed during meiosis [scRNA-seq & scATAC-seq]

2025-05-10 | GSE296438 | GEO

Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at the promoters of genes expressed during meiosis [ATAC-seq]

2025-05-10 | GSE295941 | GEO

Whole-genome nucleosome mapping in meiotic diploid S. cerevisiae

Project description:We determined nucleosome positions throughout the genome in diploid S. cerevisiae undergoing early stages of synchronous meiosis. This study sought to assess if systematic reorganization of nucleosomes occurs during meiotic prophase at or near sites of DNA double strand break formation.

2011-03-07 | GSE26452 | GEO

CTCF-RNA interactions orchestrate cell-specific chromatin loop organization [MicroC]

Project description:CCCTC-binding factor (CTCF) is essential for chromatin organization, but its role in dynamically shaping chromatin loops during cellular differentiation is not fully understood. We previously demonstrated that CTCF interacts with endogenous RNAs, and deletion of its ZF1 RNA-binding region disrupts chromatin loops in mouse embryonic stem cells (ESCs). Using an ESC-to-neural progenitor cell (NPC) differentiation model, we show that the ZF1 RNA-binding region of CTCF is crucial for maintaining cell-type specific chromatin loops. Expression of CTCF-∆ZF1 leads to dysregulation of genes within these disrupted loops, particularly those involved in neuronal development and function. We identified NPC-specific, CTCF-interacting RNAs and chose Podxl and Grb10 for further study. We found that CRISPR-Cas9-mediated truncation of Podxl and Grb10 disrupts chromatin loops in cis, similar to the disruption seen in the NPC-∆ZF1 mutant. Our study underscores the importance of CTCF-ZF1 RNA interactions in preserving cell-specific genome structure and cellular identity.

2025-03-19 | GSE287376 | GEO

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