Biology subjects

Ostlund Farrants, A.-K.

Publications and source records attributed to Ostlund Farrants, A.-K..

3 recordsLinked to original sources

bioRxiv2026

Active maintenance of accessible chromatin at poised meiotic promoters by the NFYA-NURF axis is required for meiotic entry in mice

Developmental genes often acquire accessible chromatin prior to their activation, yet the mechanisms regulating this permissive state remain poorly understood. During spermatogenesis, many meiotic gene promoters display this poised state in spermatogonia, characterized by accessible promoters and paused RNA Pol II occupancy before their activation during meiosis. Here, we identify the NURF chromatin remodeling complex, comprised of SMARCA5 and its accessory subunit BPTF, as a key regulator of this process. We demonstrate that the transcription factor NFYA interacts with SMARCA5 and is required for its occupancy at poised meiotic gene promoters. Approximately one-third of poised meiotic gene promoters is co-occupied by NFYA, SMARCA5, and BPTF. Germline deletion of Smarca5 disrupts chromatin accessibility at poised meiotic promoters, impairs transcriptional program required for mitosis-to-meiosis transition, resulting in developmental arrest at meiotic entry. These findings identify NFYA-NURF as a key regulatory axis that regulates accessible chromatin at developmentally poised meiotic genes and primes them for activation later during meiosis.

developmental biology↗

bioRxiv2024

Malaria-derived hemozoin alters chromatin remodelling and skews dendritic cell responses to subsequent bacterial infections

Hemozoin (HZ), the malaria pigment, is released together with the with the parasite merozoites during the blood stage of the disease, which is connected with the pro-inflammatory response to induce T-cells and B-cells. Co-infections with bacteria lead to a more severe disease progression and the underlying mechanisms are poorly understood. Here, we investigated the impact of HZ on the early response of monocyte-derived dendritic cells (moDC) to a common bacterial component, LPS. A short-term HZ exposure for two hours did not induce an inflammatory response, but it did alter the transcriptional response to LPS. In moDC co-exposed to HZ and LPS, the induction of HLA-DR and PD-L1 gene expression was reduced and associated with decreased binding of RELA compared to LPS-stimulated cells. These gene promoters recruited the silencing chromatin remodelling complex NuRD upon co-exposure, instead of the PBAF complex at the promoter in LPS-stimulated cells. Further, HZ maintained transcription of C-type lectin receptors associated to an immature DC phenotype, DC-SIGN (CD209) and macrophage mannose receptor (MMR/CD206). Here, activated RELA and IRF3 were recruited in a PBAF and ncBAF dependent manner. Upon LPS co-exposure, NuRD was replacing these complexes to allow for a reduced transcriptional level of these immature markers. The association of chromatin remodelling complexes did not alter the chromatin state at the promoters, which was changed during differentiation to DCs or even at an earlier point. In conclusion, HZ exposure primes specific gene promoters at an early time point, which results in a different transcriptional response and may also lead to a changed immune reaction to bacterial co-infections. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/585548v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1573c58org.highwire.dtl.DTLVardef@3aeb6forg.highwire.dtl.DTLVardef@36f4bdorg.highwire.dtl.DTLVardef@1fddcd2_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Seqpac: A New Framework for small RNA analysis in R using Sequence-Based Counts

Small RNA sequencing (sRNA-seq) has become important for studying regulatory mechanisms in many cellular processes. Data analysis remains challenging, mainly because each class of sRNA--such as miRNA, piRNA, tRNA- and rRNA-derived fragments (tRFs/rRFs)--needs special considerations. Analysis therefore involves complex workflows across multiple programming languages, which can produce research bottlenecks and transparency issues. To make analysis of sRNA more accessible and transparent we present seqpac: a tool for advanced group-based analysis of sRNA completely integrated in R. This opens advanced sRNA analysis for Windows users--from adaptor trimming to visualization. Seqpac provides a framework of functions for analyzing a PAC object, which contains 3 standardized tables: sample phenotypic information (P), sequence annotations (A), and a counts table with unique sequences across the experiment (C). By applying a sequence-based counting strategy that maintains the integrity of the fastq sequence, seqpac increases flexibility and transparency compared to other workflows. It also contains an innovative targeting system allowing sequence counts to be summarized and visualized across sample groups and sequence classifications. Reanalyzing published data, we show that seqpacs fastq trimming performs equal to standard software outside R and demonstrate how sequence-based counting detects previously unreported bias. Applying seqpac to new experimental data, we discovered a novel rRF that was down-regulated by RNA pol I inhibition (anticancer treatment), and up-regulated in previously published data from tumor positive patients. Seqpac is available on github (https://github.com/Danis102/seqpac), runs on multiple platforms (Windows/Linux/Mac), and is provided with a step-by-step vignette on how to analyze sRNA-seq data.

bioinformatics↗