Members of an array of zinc-finger proteins specify distinct Hox chromatin boundaries.

Autor:	Ortabozkoyun H; Howard Hughes Medical Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY 10016, USA. Electronic address: hxo128@miami.edu., Huang PY; Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY 10016, USA., Gonzalez-Buendia E; Howard Hughes Medical Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY 10016, USA., Cho H; Department of Pathology, NYU Langone Health, New York, NY 10016, USA; Applied Bioinformatics Laboratories, NYU Langone Health, New York, NY 10016, USA; Department of Medicine, Division of Precision Medicine, NYU Langone Health, New York, NY 10016, USA., Kim SY; Department of Pathology, NYU Langone Health, New York, NY 10016, USA., Tsirigos A; Department of Pathology, NYU Langone Health, New York, NY 10016, USA; Applied Bioinformatics Laboratories, NYU Langone Health, New York, NY 10016, USA; Institute for Computational Medicine, NYU Langone Health, New York, NY 10016, USA., Mazzoni EO; Department of Cell Biology, NYU Langone Health, New York, NY 10016, USA., Reinberg D; Howard Hughes Medical Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY 10016, USA. Electronic address: dxr1274@miami.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 Sep 19; Vol. 84 (18), pp. 3406-3422.e6. Date of Electronic Publication: 2024 Aug 21.
DOI:	10.1016/j.molcel.2024.08.007
Abstrakt:	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. Competing Interests: Declaration of interests D.R. was a co-founder of Constellation Pharmaceuticals and Fulcrum Therapeutics. Currently, D.R. has no affiliation with either company. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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