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Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs).

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Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells.

Proc Natl Acad Sci U S A

January 2025

Center for Nutritional Sciences, Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611.

Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.

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Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

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In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion.

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The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, and its dysregulation is associated with genetic disorders, physiological and premature aging, and cancer. The effects of p63 are carried out by two main isoforms that regulate cell proliferation and senescence. p63 also controls the epigenome by regulating interactions with histone modulators, such as the histone acetyltransferase p300, deacetylase HDAC1/2, and DNA methyltransferases.

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