| Autor: |
Samir Rahman, Yan Jiang, Kiran Girdhar, Haroutunian, Pengfei Dong, Mette A. Peters, E Flatow, Chang-Gyu Hahn, Stella Dracheva, John F. Fullard, Schahram Akbarian, Barbara K. Lipska, R.E. Gur, Stefano Marenco, Couto L, Elizabeth Zharovsky, Royce Park, David A. Lewis, Gabriel E. Hoffman, Bibi Kassim, Alex Kozlenkov, Panagiotis Roussos, Carol A. Tamminga, Leanne Brown, Wiseman, Jaroslav Bendl, Thomas G. Gilgenast, Will Liao, Devillers O, Jessica S. Johnson, Marija Kundakovic, Jennifer E. Phillips-Cremins, Rivka Jacobov |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.06.02.446728 |
| Popis: |
To explore modular organization of chromosomes in schizophrenia (SCZ) and bipolar disorder (BD), we applied ‘population-scale’ correlational structuring of 739 histone H3-lysine 27 acetylation and H3-lysine 4 trimethylation profiles, generated from the prefrontal cortex (PFC) of 568 cases and controls. Neuronal histone acetylomes and methylomes assembled as thousands of cis-regulatory domains (CRDs), revealing fine-grained, kilo-to megabase scale chromatin organization at higher resolution but firmly integrated into Hi-C chromosomal conformations. Large clusters of domains that were hyperacetylated in disease shared spatial positioning within the nucleus, predominantly regulating PFC projection neuron function and excitatory neurotransmission. Hypoacetylated domains were linked to inhibitory interneuron- and myelination-relevant genes. Chromosomal modular architecture is affected in SCZ and BD, with hyperacetylated domains showing unexpectedly strong convergences defined by cell type, nuclear topography, genetic risk, and active chromatin state across a wide developmental window. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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