Biology subjects

Taslim, T. H.

Publications and source records attributed to Taslim, T. H..

3 recordsLinked to original sources

bioRxiv2026

Atlas of HIV cis-regulatory elements reveals extensive transcriptional variation across clades, isolates, and within individuals

Human immunodeficiency virus (HIV) replication, persistence, and reactivation depend on transcription from integrated proviruses. Despite extensive sequence variation, how viral genetic diversity influences transcriptional regulation remains poorly understood. Here, we generate a functional regulatory atlas of HIV-1 and HIV-2 by combining tiling and saturation mutagenesis massively parallel reporter assays (MPRAs) with comparative sequence analysis and predictive modeling. By profiling thousands of HIV isolates in Jurkat and human primary CD4+T cells, we reveal extensive variation in baseline and stimulus-induced long terminal repeat (LTR) activity across and within clades, driven by distinct transcription factor configurations. These activities frequently differ among proviruses from the same individual and shift over infection and transmission without consistent selection for activity. Beyond the LTR, we identify conserved intragenic cis-regulatory elements, revealing regulatory architectures that complement LTR activity. Finally, we develop sequence-based models that accurately predict transcriptional activity, enabling scalable functional annotation of viral diversity and evolution.

microbiology↗

bioRxiv2025

Global cis-regulatory landscape of double-stranded DNA viruses

Most double-stranded DNA (dsDNA) viruses use the host transcriptional machinery to express viral genes for replication and immune evasion. This is mediated by viral cis-regulatory elements (CREs) regulated by host and viral transcription factors (TFs). Although some viral CREs and their regulatory mechanisms have been determined, most remain unidentified. Here, we used massively parallel reporter assays to identify [~]2,000 CREs across 27 dsDNA viruses from the Adenovirus, Herpesvirus, Polyomavirus and Papillomavirus families. Viral genomes have a higher CRE density than the human genome, with most viral CREs having promoter-like features and overlapping protein coding sequences. Using saturation mutagenesis and machine learning models, we report viral CRE regulators, including SP, ETS, bZIPs, and TFs acting downstream of signal-activated pathways. Altogether, we present a comprehensive functional CRE map of human-infecting dsDNA viruses that serves as a blueprint for further studies in viral regulation, reactivation, evolution, and viral vector design.

genomics↗

bioRxiv2021

Stem cell quiescence requires PRC2/PRC1-mediated mitochondrial checkpoint

Both normal and tumorous stem cells can arrest cell division, avoid apoptosis, and then regenerate lost daughter cells following acute genotoxic insult. This protective, reversible proliferative arrest, known as "quiescence," is still poorly understood. Here, we show that mTOR-regulated mitophagy is required for radiation insult-induced quiescence in Drosophila germline stem cells (GSCs). In GSCs, depletion of mito-fission (Drp1) or mitophagy (Pink1 and Parkin) eliminates entry into quiescence, while depletion of mitochondrial biogenesis (PGC1) or fusion (Mfn2) eliminates exit from quiescence. We also find that mitophagy-dependent quiescence is under epigenetic control; knockdown of Jarid2 (PRC2) or Pc or Sce (PRC1) stabilizes the mitochondria and locks GSCs out of quiescence, while knockdown of PRC2-specific demethylase, Utx, prevents re-accumulation of the mitochondria and locks GSCs in quiescence. These data suggest that mitochondrial number coordinates reversible quiescence. We further identify that the mechanism of quiescence in both GSCs and human induced pluripotent stem cells (iPSCs) relies on mitophagy to deplete the mitochondrial pool of CycE and limit cell cycle progression. This alternative method of G1/S regulation may present new opportunities for therapeutic purposes.

biochemistry↗