2024/08/23 by Havva Ortabozkoyun, Pin‐Yao Huang, Edgar González-Buendía +5 · 1 voice · 2 citations
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · #Genomics and Chromatin Dynamics #Plant Molecular Biology Research #RNA Research and Splicing
paper · doi:10.1016/j.molcel.2024.08.007
openalex publication_date 2024/08/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Partitioning of repressive from actively transcribed chromatin in mammalian cells fosters cell-type-specific gene expression patterns. While this partitioning is reconstructed during differentiation, the chromatin occupancy of the key insulator, CCCTC-binding factor (CTCF), is unchanged at the developmentally important Hox clusters. Thus, dynamic changes in chromatin boundaries must entail other activities. Given its requirement for chromatin loop formation, we examined cohesin-based chromatin occupancy without known insulators, CTCF and Myc-associated zinc-finger protein (MAZ), and identified a family of zinc-finger proteins (ZNFs), some of which exhibit tissue-specific expression. Two such ZNFs foster chromatin boundaries at the Hox clusters that are distinct from each other and from MAZ. PATZ1 was critical to the thoracolumbar boundary in differentiating motor neurons and mouse skeleton, while ZNF263 contributed to cervicothoracic boundaries. We propose that these insulating activities act with cohesin, alone or combinatorially, with or without CTCF, to implement precise positional identity and cell fate during development.