BRPF1 is essential for development of fetal hematopoietic stem cells

You, Linya; Lin, Li; Zou, Jinfeng; Kou, Yan; Belle, Jad I.; Nijnik, Anastasia; Wang, Edwin; Yang, Xiang‐Jiao

doi:10.1172/jci80711

Cited by 33 publications

(48 citation statements)

References 108 publications

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“…histone peptide, we also tested the binding affinity of this bromodomain with mono-and diacetylated peptides containing the first 24 amino acid residues of human histone H3. Earlier ITC experiments done with the H3K14ac (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and H3K9ac (1-12) peptides had KDs of 626 µM, and no binding, respectively 31 . Our current ITC experiments on the H3K14ac (1-24) and…”

Section: The Brpf1 Bromodomain Recognizes Di-acetyllysine Histone Modmentioning

confidence: 98%

“…H4K12ac (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and H4K16ac (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) with KDs of 168.4 ± 4.7 µM, 97.3 ± 4.0 µM and 464.3 ± 1.7 µM, respectively. Interestingly, when the ITC experiment was performed with the diacetylated H4K5acK8ac (1-10) peptide the BRPF1 bromodomain bound with a dissociation constant about two-fold stronger than that of the mono-acetylated H4K5ac peptide (26.7 ± 1.8 µM).…”

Section: The Brpf1 Bromodomain Recognizes Di-acetyllysine Histone Modmentioning

confidence: 99%

“…Amongst the di-acetylated histone ligands, H4K5acK8ac (1-10) and H4K5acK12ac (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) showed not only the most negative ΔH values, but also the highest binding affinities KD = 26.7 ± 1.8 µM and 52.0 ± 2.9 µM, respectively, indicating that more energetically favorable electrostatic and van der Waals interactions form with these ligands. The change in entropy (ΔS) to more negative values observed upon BRPF1 bromodomain binding to the di-acetylated histone ligands is also suggestive of favorable conformational changes that occur during the complex formation.…”

Section: Thermodynamics Of Di-acetylated Histone Ligand Binding To Thmentioning

confidence: 99%

“…Bromodomain-PHD finger protein 1 (BRPF1) is known to play a role in maintaining the expression of genes involved in several developmental processes and hematopoiesis [6][7][8] . The BPRF1 protein is a unique, multivalent chromatin reader which contains an N-terminal plant homeodomain (PHD)-zinc-knuckle-PHD (PZP) module, a bromodomain for acetyllysine recognition, and a C-terminal proline-tryptophan-tryptophan-proline (PWWP) domain 9 .…”

Section: Introductionmentioning

confidence: 99%

“…The Nterminal motif I of BRPF1 interacts with monocytic leukemic zinc finger (MOZ) and MOZrelated factor (MORF), while the downstream motif II interacts with inhibitor of growth 5 (ING5) and the MYST/Esa1-associated factor 6 (MEAF6) 10 . Thus, an important function of BRPF1 is to bridge the association of MOZ and MORF with ING5 and MEAF6, where it is an important regulator of many cellular processes including the self-renewal of leukemic stem cells 8 , embryo development and cell proliferation 11 , and osteoclast differentiation 12 through its activity with MOZ and MORF 8 . BRPF1 enhances the acetyltransferase activity of the MOZ/MORF HATs via interaction with the histone acetyltransferase domain 10 , and also bridges the enzymatic complex to specific post-translational modifications in chromatin 13 .…”

Section: Introductionmentioning

confidence: 99%

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The BRPF1 bromodomain is a molecular reader of di-acetyllysine

Juliet

Lubula

Cornilescu

et al. 2020

Preprint

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ABSTRACTBromodomain-containing proteins are often part of chromatin-modifying complexes, and their activity can lead to altered expression of genes that drive cancer, inflammation and neurological disorders in humans. Bromodomain-PHD finger protein 1 (BRPF1) is part of the MOZ (monocytic leukemic zinc-finger protein) HAT (histone acetyltransferase) complex, which is associated with chromosomal translocations known to contribute to the development of acute myeloid leukemia (AML). BRPF1 contains a unique combination of chromatin reader domains including two plant homeodomain (PHD) fingers separated by a zinc knuckle (PZP domain), a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. BRPF1 is known to recruit the MOZ HAT complex to chromatin by recognizing acetylated lysine residues on the N-terminal histone tail region through its bromodomain. However, histone proteins can contain several acetylation modifications on their N-terminus, and it is unknown how additional marks influence bromodomain recruitment to chromatin. Here, we identify the BRPF1 bromodomain as a selective reader of di-acetyllysine modifications on histone H4. We used ITC assays to characterize the binding of di-acetylated histone ligands to the BRPF1 bromodomain and found that the domain binds preferentially to histone peptides H4K5acK8ac and H4K5acK12ac. Analytical ultracentrifugation (AUC) experiments revealed that the monomeric state of the BRPF1 bromodomain coordinates di-acetylated histone ligands. NMR chemical shift perturbation studies, along with binding and mutational analyses, revealed non-canonical regions of the bromodomain-binding pocket that are important for histone tail recognition. Together, our findings provide critical information on how the combinatorial action of post-translational modifications can modulate BRPF1 bromodomain binding and specificity.

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Section: The Brpf1 Bromodomain Recognizes Di-acetyllysine Histone Modmentioning

confidence: 98%

Section: The Brpf1 Bromodomain Recognizes Di-acetyllysine Histone Modmentioning

confidence: 99%

Section: Thermodynamics Of Di-acetylated Histone Ligand Binding To Thmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The BRPF1 bromodomain is a molecular reader of di-acetyllysine

Juliet

Lubula

Cornilescu

et al. 2020

Preprint

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Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

Kose,

Kaya,

Akcan

et al. 2023

American J of Med Genetics Pt A

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Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) (MIM#617333) is an autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability (ID), and dysmorphic facial features due to pathogenic variations in the Bromodomain-and PHD Finger-Containing Protein (BRPF1) (MIM#602410) gene. Herein, we report the first Turkish patients with IDDDFP. Additionally, the patients had hematopoietic disorders such as anemia and thrombocytopenia, which have not been previously described in IDDDFP patients.Genetic testing using Whole Exome Sequencing (WES) revealed a novel heterozygous c.1433G > A; p.W478* (NM_004634.3) pathogenic variant on exon 3 of the BRPF1 gene. The patients demonstrated classical features of IDDDFP such as intellectual disability, developmental delay, ptosis, micro and retrognathia, and dysmorphic facial features, in addition to the anemia and thrombocytopenia. Apart from the variant in BRPF1, no additional genomic changes were detected by WES and chromosomal microarray analysis (CMA). Hopefully, our novel report on the hematopoietic anomalies of our patients due to BRPF1 will expand upon the clinical spectrum of IDDDFP, encourage further studies about BRPF1-hematopoietic system relations, and affect the diagnostic and therapeutic schemes of hematopoietic system disorders.

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Assays for Acetylation and Other Acylations of Lysine Residues

2017

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Lysine acetylation refers to addition of an acetyl moiety to the epsilon-amino group of a lysine residue and is important for regulating protein functions in various organisms from bacteria to humans. This is a reversible and precisely controlled covalent modification that either serves as an on/off switch or participates in a codified manner with other post-translational modifications to regulate different cellular and developmental processes in normal and pathological states. This unit describes methods for in vitro and in vivo determination of lysine acetylation. Such methods can be easily extended for analysis of other acylations (such as propionylation, butyrylation, crotonylation, and succinylation) that are also present in histones and many other proteins. © 2017 by John Wiley & Sons, Inc.

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BRPF1 is essential for development of fetal hematopoietic stem cells

Cited by 33 publications

References 108 publications

The BRPF1 bromodomain is a molecular reader of di-acetyllysine

The BRPF1 bromodomain is a molecular reader of di-acetyllysine

Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

Assays for Acetylation and Other Acylations of Lysine Residues

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