Biology subjects

Nahar, S.

Publications and source records attributed to Nahar, S..

4 recordsLinked to original sources

bioRxiv2025

A scheduler for rhythmic gene expression

Genetic oscillators drive precisely timed gene expression, crucial for development and physiology. Using the C. elegans molting clock as a model, we investigate how oscillators can schedule the orderly expression of thousands of genes. Single cell RNA sequencing reveals a broad peak phase dispersion in individual issues, mirrored by rhythmic changes in chromatin accessibility at thousands of regulatory elements identified by time-resolved ATAC-seq. We develop a linear model to predict chromatin dynamics based on the binding of >200 transcription factors. This identifies nine key regulators acting additively to determine the peak phase and amplitude of each regulatory element. Strikingly, these factors can also generate constitutive, non-rhythmic activity through destructive interference. Validating its power, the model accurately predicts the impact of GRH-1/Grainyhead perturbation on both chromatin and transcript dynamics. This work provides a conceptual framework for understanding how combinatorial, non-cooperative transcription factor binding schedules complex gene expression patterns in development and other dynamic biological processes.

systems biology↗

bioRxiv2022

A multifunctional LysM effector of Botrytis cinerea contributes to plant infection

O_LILysM effectors are suppressors of chitin-triggered plant immunity in biotrophic and hemibiotrophic fungi. Their role in necrotrophic fungi is unclear as these last are known to activate plant defenses and induce cell death. C_LIO_LITo characterize the role of the BcLysM1 gene encoding a putative LysM effector in the necrotrophic fungus Botrytis cinerea, its expression was followed by transcriptional fusion and by RT-qPCR in planta. Two tagged-recombinant proteins were produced, and two independent deletion strains were constructed and characterized. C_LIO_LIBcLysM1 is induced in the early phase of infection, and more specifically in multicellular appressoria called infection cushions. The BcLysM1 protein binds the chitin in the fungus cell wall and protects hyphae against degradation by external chitinases. It is also able to sequester chitooligosaccharides and to prevent them from inducing ROS production in A. thaliana. Using mycelium as inoculum, deletion strains show a delay in infection initiation and a default in adhesion to bean leaf surfaces. C_LIO_LIThis study demonstrates for the first time a dual role for a LysM effector in mycelium adhesion on the plant and in host defenses suppression, both of them occurring during the asymptomatic phase of infection by a necrotrophic fungus. C_LI

microbiology↗

bioRxiv2022

The Grainyhead/LSF transcription factor GRH-1 is rhythmically required for molting

Molting, that is, the synthesis and shedding of a cuticular exoskeleton, is a defining characteristic of ecdysozoa. In nematodes such as C. elegans, molts rhythmically terminate each of four larval stages. The molting cycle is tightly coupled to the rhythmic accumulation of thousands of transcripts. Here, using chromatin immunoprecipitation coupled to sequencing (ChIP-seq) and quantitative reporter assays, we show that these dynamic gene expression patterns rely on rhythmic transcription. To gain insight into the relevant gene regulatory networks (GRNs), we performed an RNAi-based screen for transcription factors required for molting to identify potential components of a molting clock. We find that depletion of GRH-1, BLMP-1, NHR-23, NHR-25, MYRF-1 or BED-3 impairs progression through the molting cycle. We characterize GRH-1, a Grainyhead/LSF transcription factor whose orthologues in other animals are key epithelial cell fate regulators. We show that GRH-1 depletion causes a dose-dependent extension of molt duration, defects in cuticle formation and shedding, and larval death. Coincident with its rhythmic accumulation, GRH-1 is required repetitively for each molt, during specific time windows preceding lethargus. These findings are consistent with a function of GRH-1 in a molting cycle GRN. As its mammalian orthologues, as well as those of BLMP-1 and NHR-23, have been implicated in rhythmic homeostatic skin regeneration in mouse, the mechanisms underlying rhythmic C. elegans molting may apply beyond nematodes.

developmental biology↗

bioRxiv2017

LEAP: A Generalization Of The Landau-Vishkin Algorithm With Custom Gap Paneities

MotivationApproximate String Matching is a pivotal problem in the field of computer science. It serves as an integral component for many string algorithms, most notably, DNA read mapping and alignment. The improved LV algorithm proposes an improved dynamic programming strategy over the banded Smith-Waterman algorithm but suffers from support of a limited selection of scoring schemes. In this paper, we propose the Leaping Toad problem, a generalization of the approximate string matching problem, as well as LEAP, a generalization of the Landau-Vishkins algorithm that solves the Leaping Toad problem under a broader selection of scoring schemes.\n\nResultsWe benchmarked LEAP against 3 state-of-the-art approximate string matching implementations. We show that when using a bit-vectorized de Bruijn sequence based optimization, LEAP is up to 7.4x faster than the state-of-the-art bit-vector Levenshtein distance implementation and up to 32x faster than the state-of-the-art affine-gap-penalty parallel Needleman Wunsch Implementation.\n\nAvailabilityWe provide an implementation of LEAP in C++ at github.com/CMU-SAFARI/LEAP.\n\nContacthxin@cmu.edu, calkan@cs.bilkent.edu.tr or onur.mutlu@inf.ethz.ch

bioinformatics↗