bioRxiv Science⌕ Search

Biology subjects

Izquierdo, J.

Publications and source records attributed to Izquierdo, J..

2 recordsLinked to original sources
bioRxiv2026

ULTRAPETALA1 remodels PRC2 recruitment to nucleosomes

Polycomb Repressive Complex 2 (PRC2) establishes transcriptional repression through trimethylation of histone H3 lysine 27 (H3K27me3), a modification essential for developmental patterning. Here, we describe a novel plant-specific PRC2 variant (PRC2.3) that employs a distinct nucleosome-targeting mechanism mediated by accessory factor ULTRAPETALA1 (ULT1), which promotes H3K27me3 deposition at over 1,300 developmental genes. The cryo-EM structure of the PRC2SWN-ULT1-nucleosome complex reveals that ULT1 antagonizes the canonical PRC2 binding mode and instead bridges PRC2 to the nucleosome using its own interaction surfaces. ULT1 binds consecutive purines in the nucleosomal DNA and the histone H2A/H2B acidic patch, while enabling PRC2 to accommodate H3K36 modifications. We further show that in planta ULT1 enhances H3K27me3 at purine-rich loci and at genes associated with H3K36 marks, and identify the ULT1-H2A/H2B interface as required for reproductive transition and flower organogenesis. Our findings demonstrate that PRC2 can deploy mechanistically distinct recruitment strategies to control key developmental switches.

Molecular Biology↗
bioRxiv2026

Distinct DNA-binding syntax and chromatin remodeling capacities of bHLH transcription factors in cell differentiation, reprogramming and cancer

Basic helix-loop-helix (bHLH) transcription factors orchestrate cell differentiation, reprogramming, and oncogenic transformation, yet the molecular determinants that govern their DNA-binding specificity and capacity to remodel chromatin remain incompletely understood. Here, we assemble and unify all available bHLH induction ChIP-seq datasets (74 experiments covering 17 factors) and integrate them with matched chromatin accessibility, nucleosome positioning, CpG methylation, transcriptomic profiling, methyl-HT-SELEX, and structural modeling. Using an exact hexanucleotide-based approach, we define the sequence grammar that shapes bHLH-DNA interactions and identify distinct motif architectures associated with binding to accessible versus inaccessible chromatin. CAT- and CAG-preferring bHLH factors--including proneural and myogenic regulators--display robust pioneer-like behavior, characterized by preferential engagement of closed chromatin through specific E-box variants, cooperative motif clustering, and characteristic spacing patterns. TWIST factors exhibit a unique 5-bp E-box periodicity linked to dedifferentiation programs, whereas CAC-preferring oncogenic bHLHs remain largely restricted to open chromatin. By integrating methylation and SELEX data, we reveal that CpG methylation drives a systematic shift from the canonical CAC-CAC motif toward CAT-CAC E-boxes, providing a mechanistic explanation for MYC enhancer invasion in cancer and uncovering parallel behavior in the HEY family. Nucleosome chemical mapping and structural predictions further show that nearly all bHLH factors bind preferentially at nucleosome flanks, independent of -helix length, challenging prior models of nucleosomal engagement. Together, these results establish a unified framework linking sequence syntax, chromatin state, and transcriptional outcome across the bHLH family, providing mechanistic principles for understanding lineage specification, reprogramming, and oncogenic enhancer remodeling.

molecular biology↗