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Linker histones function in chromosomal RNAs homeostasis and chromatin dynamics
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[eng] Linker histones are essential proteins involved in higher-order chromatin structures and architectural functions. However, their roles extend beyond structure, encompassing various chromatin metabolic processes such as DNA replication, repair, and epigenetic modulation. To unravel the functional complexity of linker histones, we chose the model organism Drosophila melanogaster due to its peculiarity of only having a single somatic variant (dH1) and one germinal/embryonic variant (dBigH1). First, we explored the consequences of dH1 depletion on chromatin structure and stability. Remarkably, depletion of dH1 resulted in genomic instability and the accumulation of RNA:DNA hybrids (R-loops) in heterochromatin. To explore the molecular mechanism behind these observed effects, we decided to study the chromosomal RNAs (cRNAs). Our findings revealed that cRNAs, a diverse group of RNA species co-purifying with chromatin, extensively covered approximately 28% of the genome. Notably, cRNAs exhibited a significant enrichment in heterochromatic transcripts and displayed strong associations with hnRNP A/B proteins hrp36 and hrp48, forming ribonucleoprotein (RNP) complexes. Intriguingly, the depletion of dH1 led to impaired assembly of hrp36 and hrp48 onto heterochromatic cRNAs, contributing to increased R-loop formation and abnormal cRNA retention. Furthermore, the altered chromatin organization resulting from dH1 depletion, characterized by reduced nucleosome occupancy and enhanced heterochromatin accessibility, facilitated the annealing of cRNAs to DNA templates. These findings provide unexpected insights into the involvement of linker histones in RNP assembly and cRNA homeostasis. The second part of this study focused on investigating the biochemical properties and the phase separation capabilities of somatic dH1 and germinal/embryonic dBigH1 linker histones. Phase separation of chromatin is a fundamental process associated with diverse chromatin functions. Our analyses demonstrated the distinct characteristics of dH1 and dBigH1 in promoting phase separation, suggesting their potential roles in different functional states of chromatin.
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BUJOSA RODRIGUEZ, Paula. Linker histones function in chromosomal RNAs homeostasis and chromatin dynamics. [consulta: 21 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/202709]