Tabar Mehdi Sharifi, Parsania Chirag, Giardina Caroline, Feng Yue, Wong Alex C H, Metierre Cynthia, Nagarajah Rajini, Dhungel Bijay P, Rasko John E J, Bailey Charles G
Faculty of Medicine & Health, The University of Sydney, Camperdown, New South Wales, Australia.
Cancer & Gene Regulation Laboratory Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.
FASEB J. 2025 May 31;39(10):e70632. doi: 10.1096/fj.202402808RR.
Chromodomain helicase DNA-binding (CHD) enzymes play a pivotal role in genome regulation. They possess highly conserved ATPase domains flanked by poorly characterized and intrinsically disordered N- and C-termini. Using mass spectrometry, we identify dozens of novel protein-protein interactions (PPIs) within the N- and C-termini of human CHD family members. We also define a highly conserved aggregation-prone region (APR) within the C-terminus of CHD4 which is critical for its interaction with the nucleosome remodeling and deacetylase (NuRD), as well as ChAHP (CHD4, activity-dependent neuroprotective protein (ADNP), and HP1γ) complexes. Further analysis reveals a regulatory role for the CHD4 APR in gene transcription during erythrocyte formation. Our results highlight that the N- and C-termini of CHD chromatin remodelers shape protein interaction networks that drive unique transcriptional programs.
染色质结构域解旋酶DNA结合（CHD）酶在基因组调控中起关键作用。它们拥有高度保守的ATP酶结构域，两侧是特征不明且内在无序的N端和C端。通过质谱分析，我们在人类CHD家族成员的N端和C端鉴定出数十种新的蛋白质-蛋白质相互作用（PPI）。我们还在CHD4的C端定义了一个高度保守的易聚集区域（APR），该区域对于其与核小体重塑和去乙酰化酶（NuRD）以及ChAHP（CHD4、活性依赖性神经保护蛋白（ADNP）和HP1γ）复合物的相互作用至关重要。进一步分析揭示了CHD4 APR在红细胞形成过程中对基因转录的调控作用。我们的结果突出表明，CHD染色质重塑因子的N端和C端塑造了驱动独特转录程序的蛋白质相互作用网络。
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