Last update 19 Sep 2024

BRPF1

Last update 19 Sep 2024

Basic Info

Synonyms

BR140, bromodomain and PHD finger containing 1, bromodomain and PHD finger containing, 1

+ [5]

Introduction

Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:24065767, PubMed:27939640). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac) (PubMed:24065767). Some HAT complexes preferentially mediate histone H3 'Lys-23' (H3K23ac) acetylation (PubMed:27939640). Positively regulates the transcription of RUNX1 and RUNX2 (PubMed:18794358).

Drugs associated with BRPF1

GSK6853

Target

BRPF1

Mechanism

BRPF1 inhibitors

Active Org.

GSK Plc

Originator Org.

GSK Plc

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NI-57

Target

BRPF1 x BRPF2

Mechanism

BRPF1 inhibitors [+1]

Active Org.

University College London

Originator Org.

University College London

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NUE-20798

Target

BRPF1

Mechanism

BRPF1 inhibitors

Active Org.-

Originator Org.

Nuevolution AB

Active Indication-

Inactive Indication

Dermatitis, Atopic

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with BRPF1

100 Translational Medicine associated with BRPF1

0 Patents (Medical) associated with BRPF1

Literatures (Medical) associated with BRPF1

01 May 2024·Neural regeneration research

Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory.

Article

Author: Liu, Ying ; You, Linya ; Zhang, Hang ; Liu, Shuai ; Hu, Jiayi ; Zu, Gaoyu ; Zhao, Baicheng ; Zhang, Yuxiao

Bromodomain and plant homeodomain (PHD) finger containing protein 1 (Brpf1) is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase (KAT) 6A/6B/7. Brpf1, KAT6A, and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability. Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain, especially the hippocampus, which has essential roles in learning and memory. Here, we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons, and that its deficiency leads to learning and memory deficits. To test this, we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre. We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1, Slc16a7, Robo3, and Rho, which are related to neural development, synapse function, and memory, thereby damaging spatial and fear memory in mice. These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

01 Apr 2024·European Journal of Medical Genetics

Beyond 'speech delay': Expanding the phenotype of BRPF1-related disorder

Article

Author: Morison, Lottie D ; Van Reyk, Olivia ; Amor, David J ; Ruaud, Lyse ; Couque, Nathalie ; Baker, Emma ; Morgan, Angela T ; Verloes, Alain

Pathogenic variants in BRPF1 cause intellectual disability, ptosis and facial dysmorphism. Speech and language deficits have been identified as a manifestation of BRPF1-related disorder but have not been systematically characterized. We provide a comprehensive delineation of speech and language abilities in BRPF1-related disorder and expand the phenotype. Speech and language, and health and medical history were assessed in 15 participants (male = 10, median age = 7 years 4 months) with 14 BRPF1 variants. Language disorders were common (11/12), and most had mild to moderate deficits across receptive, expressive, written, and social-pragmatic domains. Speech disorders were frequent (7/9), including phonological delay (6/9) and disorder (3/9), and childhood apraxia of speech (3/9). All those tested for cognitive abilities had a FSIQ ≥70 (4/4). Participants had vision impairment (13/15), fine (8/15) and gross motor delay (10/15) which often resolved in later childhood, infant feeding impairment (8/15), and infant hypotonia (9/15). We have implicated BRPF1-related disorder as causative for speech and language disorder, including childhood apraxia of speech. Adaptive behavior and cognition were strengths when compared to other monogenic neurodevelopmental chromatin-related disorders. The universal involvement of speech and language impairment is noteable, relative to the high degree of phenotypic variability in BRPF1-related disorder.

01 Jan 2024·Journal of Biological Chemistry

Uncovering the non-histone interactome of the BRPF1 bromodomain using site-specific azide-acetyllysine photochemistry

Article

Author: Sudhamalla, Babu ; Barman, Soumen ; Padhan, Jyotirmayee

Bromodomain-PHD finger protein 1 (BRPF1) belongs to the BRPF family of bromodomain-containing proteins. Bromodomains are exclusive reader modules that recognize and bind acetylated histones and non-histone transcription factors to regulate gene expression. The biological functions of acetylated histone recognition by BRPF1 bromodomain are well characterized; however, the function of BRPF1 regulation via non-histone acetylation is still unexplored. Therefore, identifying the non-histone interactome of BRPF1 is pivotal in deciphering its role in diverse cellular processes, including its misregulation in diseases like cancer. Herein, we identified the non-histone interacting partners of BRPF1 utilizing a protein engineering-based approach. We site-specifically introduced the unnatural photo-cross-linkable amino acid 4-azido-L-phenylalanine into the bromodomain of BRPF1 without altering its ability to recognize acetylated histone proteins. Upon photoirradiation, the engineered BRPF1 generates a reactive nitrene species, cross-linking interacting partners with spatio-temporal precision. We demonstrated the robust cross-linking efficiency of the engineered variant with reported histone ligands of BRPF1 and further used the variant reader to cross-link its interactome. We also characterized novel interacting partners by proteomics, suggesting roles for BRPF1 in diverse cellular processes. BRPF1 interaction with interleukin enhancer-binding factor 3, one of these novel interacting partners, was further validated by isothermal titration calorimetry and co-IP. Lastly, we used publicly available ChIP-seq and RNA-seq datasets to understand the colocalization of BRPF1 and interleukin enhancer-binding factor 3 in regulating gene expression in the context of hepatocellular carcinoma. Together, these results will be crucial for full understanding of the roles of BRPF1 in transcriptional regulation and in the design of small-molecule inhibitors for cancer treatment.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

BRPF1

Basic Info

Related

Analysis