Proteomics

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Unique Protein Interaction Networks Define The Chromatin Remodeling Module of The NuRD Complex


ABSTRACT: The combination of four proteins and their paralogues including MBD2/3, GATAD2A/B, CDK2AP1, and CHD3/4/5, which we refer to as the MGCC module, form the chromatin remodeling module of the Nucleosome Remodeling and Deacetylase (NuRD) complex. To date, mechanisms by which the MGCC module acquires paralogue-specific function and specificity have not been addressed. Understanding the protein-protein interaction (PPI) network of the MGCC subunits is essential in defining underlying mechanisms of gene regulation. Therefore, using pulldown followed by mass spectrometry analysis (PD-MS) we report a proteome-wide interaction network of the MGCC module in a paralogue-specific manner. Our data also demonstrate that the disordered C-terminal region of CHD3/4/5 is a gateway to incorporate remodeling activity into both the ChAHP (CHD4, ADNP, HP1γ) and NuRD complexes in a mutually exclusive manner. We define a short aggregation prone region (APR) within the C-terminal segment of GATAD2B that is essential for the interaction of CHD4 and CDK2AP1 with the NuRD complex. Finally, we also report an association of CDK2AP1 with the Nuclear Receptor Co-Repressor (NCOR) complex. Overall, this study provides insight into the possible mechanisms through which the MGCC module can achieve specificity and diverse biological functions.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Diploid Cell

SUBMITTER: mehdi Sharifi tabar  

LAB HEAD: John Rasko

PROVIDER: PXD025263 | Pride | 2023-03-11

REPOSITORIES: Pride

Dataset's files

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Action DRS
CTRL_R1.raw Raw
CTRL_R2.raw Raw
CTRL_R3.raw Raw
CTRL_R4.raw Raw
CTRL_R5.raw Raw
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Publications

Unique protein interaction networks define the chromatin remodelling module of the NuRD complex.

Sharifi Tabar Mehdi M   Giardina Caroline C   Feng Yue Y   Francis Habib H   Moghaddas Sani Hakimeh H   Low Jason K K JKK   Mackay Joel P JP   Bailey Charles G CG   Rasko John E J JEJ  

The FEBS journal 20210731 1


The combination of four proteins and their paralogues including MBD2/3, GATAD2A/B, CDK2AP1 and CHD3/4/5, which we refer to as the MGCC module, form the chromatin remodelling module of the nucleosome remodelling and deacetylase (NuRD) complex. To date, mechanisms by which the MGCC module acquires paralogue-specific function and specificity have not been addressed. Understanding the protein-protein interaction (PPI) network of the MGCC subunits is essential for defining underlying mechanisms of ge  ...[more]

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