Biology subjects

Raingeval, M.

Publications and source records attributed to Raingeval, M..

3 recordsLinked to original sources

bioRxiv2024

NPM1 mediates genome-nucleolus interactions and the establishment of their repressive chromatin states

Repressive chromatin domains are often located at the nuclear lamina (NL) or nucleolus. Although nucleolar associated domains (NADs) have been recently mapped, the mechanisms of NAD association with nucleoli and the functional significance of their localization remain unclear. Here, we show that NAD association with nucleoli is mediated by nucleophosmin (NPM1), a factor located within the granular component, the outer layer of the nucleolus. NPM1 binds NADs, interacts with the histone lysine methyltransferase G9a (EHMT2), and is required for establishing H3K9me2 at NADs. Loss of NPM1 or expression of NPM1 mutant lacking the DNA binding domain (NPM1{Delta}DBD) caused NAD dissociation from nucleoli and H3K9me2 reduction specifically at NADs. G9a is dispensable for NAD contacts with nucleoli and interacts with NPM1{Delta}DBD, indicating that NADs acquire G9a-mediated H3K9me2 only after associating with NPM1 at nucleoli. The results provide mechanistic insights into how genomic domains associate with nucleoli and acquire their repressive chromatin state. Additionally, our findings suggest that the nucleolus not only serves as a scaffold for positioning repressive chromatin domains but also plays a direct role in establishing these chromatin states.

molecular biology↗

bioRxiv2024

Single-cell dynamics of genome-nucleolus interactions captured by nucleolar laser microdissection (NoLMseq)

Gene position in the nuclear space plays an important role in gene regulation. This is exemplified by repressive chromatin domains frequently contacting nuclear lamina or nucleoli. The nucleolus undergoes structural changes in response to various cellular states, potentially impacting genome organization. However, how the 3D-genome organization responds to nucleolar states has remained underinvestigated due to the lack of methods able to identify nucleolar associated domains (NADs) in single cells and under nucleolar stress. To address this, we developed NoLMseq, a method combining laser-capture microdissection and DNA sequencing to map NADs in single cells. NoLMseq identified many unexplored features of chromosome organization around single nucleoli such as NAD heterogeneity among ESCs, culminating in two major populations with distinct chromatin states. NADs prevalently contact nucleoli in a monoallelic manner and allelic nucleolar contact frequency mirrors gene expression and chromatin states. NoLMseq also revealed how chromosomes reorganise around nucleoli under nucleolar stress conditions, highlighting the importance of nucleolus integrity in genome organization and 3D-genome response to nucleolar stress. The results demonstrated that NoLMseq accurately measures chromosome contacts around single healthy and stressed nucleoli and it will be a critical tool to study NADs within biological populations and determine how the 3D-genome responds to nucleolar stress in healthy and disease states.

genomics↗

bioRxiv2023

Retrotransposon-driven environmental regulation of FLC leads to adaptive response to herbicide

The mobilization of retrotransposons yields major-effect mutations. Here, we report an adaptive retrotransposon insertion within the first intron of the Arabidopsis floral-repressor locus FLOWERING LOCUS C (FLC). The insertion-mutation augments the environmental sensitivity of FLC by affecting the balance between coding and non-coding transcript isoforms in response to environmental threads. We show that this balance is modulated epigenetically by DNA methylation and orchestrated by IBM2, a factor involved in the processing of intronic heterochromatin. The stress-sensitive allele of FLC has recently spread across populations subjected to recurrent chemical weeding, and we demonstrate that retrotransposon-driven acceleration of life cycle represents a rapid response to herbicide. Our findings illustrate how retrotransposition can create environmentally-sensitive alleles that facilitate adaptation to anthropogenic disturbances of the environment.

plant biology↗