Biology subjects

Azorin, F.

Publications and source records attributed to Azorin, F..

5 recordsLinked to original sources

bioRxiv2026

Coordinated regulation of Barrier-to-Autointegration Factor (BAF) phosphorylation by protein phosphatases PP2A and PP4

Phosphorylation is crucial for the regulation of Barrier-to-Autointegration Factor (BAF), a conserved nuclear envelope (NE)-associated protein that, among its diverse functions, binds chromatin and mediates its anchoring to the NE. In interphase, cycles of BAF phosphorylation, which inhibits chromatin binding, and dephosphorylation, which restores it, are essential for the dynamic anchoring of chromatin to the NE. During mitosis, BAF becomes highly phosphorylated and dissociates from chromatin, except for a small centromeric pool (cenBAF). Upon mitotic exit, BAF is dephosphorylated and re-associates with chromosomes. Two Ser/Thr protein phosphatases, PP2A and PP4, are known to dephosphorylate BAF, but their specific roles in regulating BAF phosphorylation are not yet fully understood. Here, we show that PP2A is the main phosphatase driving BAF dephosphorylation in interphase, whereas PP4 plays a minor role. During mitosis, both PP2A and PP4 localize to centromeres; however, only PP4 directly interacts with cenBAF, suggesting that it maintains this fraction in an unphosphorylated state. Notably, PP4s centromeric localization depends on PP2A. At mitotic exit, PP2A dephosphorylates the large pool of mitotically phosphorylated BAF, while PP4 controls the timing of its re-association with chromatin. Together, these findings reveal a coordinated interplay between PP2A and PP4 in controlling BAF dephosphorylation and function.

Molecular Biology↗

bioRxiv2023

Somatic chromosome pairing has a determinant impact on 3D 1 chromatin organization

In the nucleus, chromatin is intricately structured into multiple layers of 3D organization important for genome activity. How distinct layers influence each other is not well understood. In particular, the contribution of chromosome pairing to 3D chromatin organization has been largely neglected. Here, we address this question in Drosophila, an organism that shows robust chromosome pairing in interphasic somatic cells. The extent of chromosome pairing depends on the balance between pairing and anti-pairing factors, with the anti-pairing activity of the CAP-H2 condensin II subunit being the best documented. Here, we identify the zinc-finger protein Z4 as a strong anti-pairer that interacts with and mediates the chromatin binding of CAP-H2. We also report that hyperosmotic cellular stress induces fast and reversible chromosome unpairing that depends on Z4/CAP-H2. And, most important, by combining Z4 depletion and osmostress, we show that chromosome pairing reinforces intrachromosomal 3D interactions. On the one hand, pairing facilitates RNAPII occupancy that correlates with enhanced intragenic gene-loop interactions. In addition, acting at a distance, pairing reinforces chromatin-loop interactions mediated by Polycomb (Pc). In contrast, chromosome pairing does not affect which genomic intervals segregate to active (A) and inactive (B) compartments, with only minimal effects on the strength of A-A compartmental interactions. Altogether, our results unveil the intimate interplay between inter-chromosomal and intra-chromosomal 3D interactions, unraveling the interwoven relationship between different layers of chromatin organization and the essential contribution of chromosome pairing.

genomics↗

bioRxiv2021

Linker histone dH1K27 dimethylation marks Drosophila heterochromatin independently of H3K9 methylation

Post-translational modifications (PTMs) of histones are important epigenetic determinants and specific core histones PTMs correlate with functional chromatin states. However, despite linker histone H1s are heavily post-translationally modified, little is known about the genomic distribution of H1s PTMs and their association with epigenetic chromatin states. Here, we address this question in Drosophila that encodes a single somatic linker histone, dH1. We previously reported that dH1 is dimethylated at K27 (dH1K27me2). Here, we show that dH1K27me2 is a major PTM of Drosophila heterochromatin. At mitosis, dH1K27me2 accumulates at pericentromeric heterochromatin, while, in interphase cells, it is also detected at intercalary heterochromatin. ChIPseq experiments show that dH1K27me2 enriched regions cluster at both the assembled and unassembled heterochromatin regions of all four Drosophila chromosomes. More than 98% of the dH1K27me2 enriched regions map to heterochromatic repetitive DNA elements, including transposable elements, simple DNA repeats and satellite DNAs. We also show that dH1K27me2 is independent of H3K9 methylation, as it is equally detected in flies carrying a H3K9R mutation. Moreover, dH1K27me2 is not affected by depletion of Su(var)3-9, HP1a and Su(var)4-20. Altogether these results suggest that dH1K27me2 is a novel epigenetic mark of Drosophila heterochromatin that acts upstream of the major Su(var)3-9/HP1a pathway of heterochromatin formation.

molecular biology↗

bioRxiv2020

In response to Li et al.: Linker histones function in Drosophila embryogenesis

In an earlier paper (Perez-Montero et al., 2013), we reported that the embryonic linker histone of Drosophila dBigH1 was essential for early Drosophila embryogenesis since embryos homozygous for the bigH1100 mutation showed strong defects and did not survive beyond zygotic genome activation (ZGA) at cellularization. Recent results challenge these observations since null bigH1 mutations generated by CRISPR/Cas9 methodology turn out to be homozygous viable, as reported in Li et al. (2019) and here. In this regard, Li et al. described a novel mechanism by which lack of dBigH1 is compensated by the early expression of maternal dH1. Here, we confirm this observation and show that such compensatory mechanism is not activated in bigH1100 embryos.

molecular biology↗

bioRxiv2018

chroGPS 2.0: differential analysis of epigenome maps in R.

1In the last years, after systematic mapping of epigenomics data from multiple organisms, tissues and cell lines, the ability to efficiently integrate, visualize and compare such information remains a challenge. Here we present chroGPS version 2, a major update of our previously developed software chroGPS, for visualization and differential analysis of epigenomes. Methods are provided for efficient integration and comparison of data from different conditions or biological backgrounds, accounting and adjusting for systematic biases in order to provide an efficient and statistically robust base for differential analysis. We also include functionalities for general data assessment and quality control prior to comparing maps, such as functions to study chromatin domain conservation between epigenomic backgrounds, to detect gross technical outliers and also to help in the selection of candidate marks for de-novo epigenome mapping.\n\nAvailabilityhttps://www.bioconductor.org/packages/release/bioc/html/chroGPS.html - Contact: oscar.reina@irbbarcelona.org

bioinformatics↗