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Grand Lab

@grandlab.bsky.social

We are a group at the Center for Molecular Biology (ZMBH) at Heidelberg University that strive to understand the regulatory principals that govern gene expression in health and disease

15 Posts146 Follower114 Folgt
Teif lab@teiflab.bsky.social · 4w ago

Chen et al 2026. Genome-wide rotational and translational phasing of nucleosomes with human transcription factors www.cell.com/molecular-ce... ▶️ In vivo nucleosome phasing measured on the same TF-bound DNA molecule ▶️ Phasing around CTCF sites is DNA encoded ▶️ FoxA and NFIA phase adjacent nucleosomes

How transcription factors (TFs) and their binding sites organize and engage nucleosomes at natural genomic locations remains poorly understood. Here, we develop Benzonase-seq to measure the rotational phasing of nucleosomes in human cells and enhance chromatin immunoprecipitation (ChIP)-exo (v6) to measure rotational phasing on the same DNA molecule bound by a TF. Unbound CTCF sites were found to be rotationally accessible on nucleosomes, and this rotational accessibility is encoded by classical dinucleotide periodicities. CTCF binding results in nucleosome displacement to adjacent DNA phasing sequences. Upon examining 40 TF classes, unbound sites were found to be phased either inward or outward or to lack phasing. In all examined cases, TF binding (e.g., NFIA and FoxA) results in adjacent rotational and translational phasing, which is not dinucleotide encoded. Benzonase-seq also more robustly maps nucleosome and subnucleosome positions in hard-to-map CpG islands. These findings provide a clearer view of how TFs engage and position nucleosomes to shape the natural chromatin landscape.
Martina Capriati@martinacapriati.bsky.social · 3mo ago

Exciting news 📣 The first preprint from @grandlab.bsky.social is out 🧬 How are essential genes controlled? By rapid degradation and recovery of TFs alone or in combination, we show that essential genes rely on a single dominant TF, despite dense co-binding. www.biorxiv.org/content/10.6...

Essential genes are dominantly activated by single transcription factors

Cell viability depends on the precise expression of essential genes, which are controlled by CpG-island (CGI) promoters densely bound by transcription factors (TFs). This has led to the prevailing model that TFs cooperate to ensure ubiquitous expression. Here, using rapid and reversible single and combinatorial degradation in murine stem cells, we systematically dissect the regulatory interactions between five key TFs. We uncover an unexpectedly specific architecture in which regulatory dominance, rather than cooperation, is the prevailing mode, where individual TFs autonomously drive chromatin opening and gene activation at largely distinct promoters. Cooperative regulation occurs at a minority of sites with antagonistic or synergistic outcomes modulated by the interplay between nucleosome positioning and TF sensitivity to chromatin. This logic is recapitulated at synthetic sequences and reflected in human genetic variation. These findings reveal that single TFs dominantly activate distinct sets of CGI-linked genes, including essential genes, across development, homeostasis, and disease. ### Competing Interest Statement The authors have declared no competing interest. DFG, GR 6341/2-1, 556634773

biorxiv.org