PATZ1 remodels the nucleosome landscape to promote chromatin accessibility in injured neurons

Adult central nervous system neurons fail to regenerate after injury, in part due to epigenetic constraints that maintain a growth-restrictive chromatin state. We previously showed that the transcription factor PATZ1 reprograms chromatin accessibility in injured corticospinal neurons and primes the regeneration associated gene loci, but the underlying mechanism remained unclear. Here we use nucleosome-resolution profiling to reveal that PATZ1 induces widespread nucleosome eviction at regeneration-associated gene loci.

PATZ1 overexpression (PATZ1 OE) dramatically reduces both nucleosome occupancy and fuzziness, indicating active chromatin reorganization rather than passive destabilization. This reorganization occurs preferentially at distal regulatory elements, where PATZ1 drives a greater than 3-fold expansion of H3K27ac-marked active enhancers. Nucleosome eviction at these sites likely helps in enhancer activation, establishing a mechanistic link between chromatin reorganization and transcriptional reprogramming.

Our findings demonstrate that targeted nucleosome eviction at enhancers underlies PATZ1-mediated chromatin reorganization, providing mechanistic insight into the epigenetic barriers that constrain regenerative gene expression in the central nervous system (CNS). We thank CSIR-CCMB for providing research facilities and support staff.We are grateful for our LTS staff member, Venkatesh Warlu for his assistance. We extend our thanks to the funding agencies Council of Scientific and Industrial Research (CSIR) (HCP53201), Department of Biotechnology (DBT) (BT/PR51467/MED/122/358/2024), and Science Engineering Research Board (SERB) (SRG00116), ANRF-SRG, ANRF-ARG, CSIR Neuromission, ICMR and BFIBiome.

These authors contributed equally: Netra Krishna, Anisha S. Council of Scientific and Industrial Research (CSIR) – Centre for Cellular and Molecular Biology (CCMB), Hyderabad, Telangana, India Netra Krishna, Anisha S. Menon, Manojkumar Kumaran, Dhruva Kumar Kesireddy & Ishwariya Venkatesh Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India The authors declare no competing interests.

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