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Daniil M Prigozhin

Publications and source records attributed to Daniil M Prigozhin.

2 recordsLinked to original sources

The Annotated Blueprint: Integrated Functional Genomic Resources for a model Tetraploid Wheat Triticum turgidum cv. Kronos.

Triticum turgidum cv. Kronos is a tetraploid wheat cultivar that underpins one of the richest community platforms for functional genomics. Over the past decade, about 3,000 exome- and promoter-capture datasets, linked to mutagenized seed stocks, and transcriptomic and phenotypic resources have accumulated, yet the absence of a reference genome has constrained their impact. Here, we present a chromosome-scale reference genome of Kronos with high-confidence annotations, including manual curation of over 1,000 disease resistance (NLR) genes. This reference revealed previously hidden NLR diversity and clarified their genomic organization at chromosomal ends. Re-analysis of exome- and promoter-capture datasets enabled high-resolution mutation discovery in genes and regulatory regions that were previously inaccessible, uncovering the full standing variation present in Kronos mutant lines. We further re-curated transcriptomic and small RNA datasets, generating improved, genome-wide maps of microRNAs and phasiRNAs important for wheat development. Collectively, these resources elevate Kronos to reference quality and establish it as a versatile platform for functional and translational wheat research.

Journal Article

Structure and Methyl-lysine Binding Selectivity of the HUSH Complex Subunit MPP8.

The Human Silencing Hub (HUSH) guards the genome from the pathogenic effects of retroelement expression. Composed of MPP8, TASOR, and Periphilin-1, HUSH recognizes actively transcribed retrotransposed sequences by the presence of long (>1.5-kb) nascent transcripts without introns. HUSH recruits effectors that alter chromatin structure, degrade transcripts, and deposit transcriptionally repressive epigenetic marks. Here, we report the crystal structure of the C-terminal domain (CTD) of MPP8 necessary for HUSH activity. The MPP8 CTD consists of five ankyrin repeats followed by a domain with structural homology to the PINIT domains of Siz/PIAS-family SUMO E3 ligases. AlphaFold3 modeling of the MPP8-TASOR complex predicts that a SPOC domain and a domain with a novel fold in TASOR form extended interaction interfaces with the MPP8 CTD. Point mutations at these interfaces resulted in loss of HUSH-dependent transcriptional repression in a cell-based reporter assay, validating the AlphaFold3 model. The MPP8 chromodomain, known to bind the repressive mark H3K9me3, bound with similar or higher affinity to sequences in the H3K9 methyltransferase subunits SETDB1, ATF7IP, G9a, and GLP. Hence, MPP8 promotes heterochromatinization by recruiting H3K9 methyltransferases. Our work identifies novel structural elements in MPP8 required for HUSH complex assembly and silencing, thereby fulfilling vital functions in controlling retrotransposons.

Humans