PXD038798

PXD038798 is an original dataset announced via ProteomeXchange.

Title	Structural insights into p300 regulation and acetylation-dependent genome organisation
Description	Histone modifications are deposited by chromatin modifying enzymes and read out by proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of the acetyl lysine reader BRD4 that binds to the acetylase p300 and enables formation of long-range intra- and interchromosomal interactions. We here examine how acetylation reading and writing enable formation of such interactions. We show that NUT contains an acidic transcriptional activation domain that binds to the TAZ2 domain of p300. We use NMR to investigate the structure of the complex and found that the TAZ2 domain has an autoinhibitory role for p300. NUT-TAZ2 interaction or mutations found in cancer that interfere with autoinhibition by TAZ2 allosterically activate p300. p300 activation results in a self-organizing, acetylation-dependent feed-forward reaction that enables long-range interactions by bromodomain multivalent acetyl-lysine binding. We discuss the implications for chromatin organisation, gene regulation and dysregulation in disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:43:34.593.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniel Panne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-13 05:58:25	ID requested
1	2023-03-11 10:33:26	announced
⏵ 2	2023-11-14 08:43:35	announced	2023-11-14: Updated project metadata.

Ibrahim Z, Wang T, Destaing O, Salvi N, Hoghoughi N, Chabert C, Rusu A, Gao J, Feletto L, Reynoird N, Schalch T, Zhao Y, Blackledge M, Khochbin S, Panne D, Structural insights into p300 regulation and acetylation-dependent genome organisation. Nat Commun, 13(1):7759(2022) [pubmed]

submitter keyword: p300, nucleosome, Acetylation

Daniel Panne
contact affiliation	University of Leicester
contact email	daniel.panne@le.ac.uk
lab head
Daniel Panne
contact affiliation	University of Leicester
contact email	daniel.panne@le.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD038798

PRIDE project URI

• PRIDE
  1. PXD038798
     1. Label: PRIDE project
     2. Name: Structural insights into p300 regulation and acetylation-dependent genome organisation