Deficiency of the Chromatin Regulator Brpf1 Causes Abnormal Brain Development

You, Linya; Zou, Jinfeng; Zhang, Hong; Bertos, Nicholas; Park, Morag; Wang, Edwin; Yang, Xiang‐Jiao

doi:10.1074/jbc.m114.635250

Cited by 50 publications

(90 citation statements)

References 84 publications

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“…␤-Gal Staining of Placental Sections-The staining procedure was the same as described (38,39,47). Briefly, pregnant mice were euthanized, and placentae were dissected out and fixed in 1% paraformaldehyde at 4°C for 1-2 h. After washing with PBS, placentae were further cryoprotected in 30% sucrose in PBS overnight at 4°C, embedded in Tissue-Tek OCT compound (Sakura Finetek, 4583) on dry ice, and stored at Ϫ80°C.…”

Section: Methodsmentioning

confidence: 99%

“…These results reveal that Brpf1 regulates different developmental programs during embryogenesis and that it is important for growth and proliferation of embryonic fibroblasts and hematopoietic progenitors. While two recent reports are on the crucial function of Brpf1 in mouse forebrain development (39,40), this study identifies an essential role in regulating developmental programs just before mid-gestation. These new findings are unexpected from published genetic studies of mouse Moz, Morf, and Hbo1 (41)(42)(43)(44).…”

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confidence: 99%

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The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation

You

Kou

Zou

et al. 2015

Journal of Biological Chemistry

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Background: Deletion of the mouse Brpf1 gene causes embryonic lethality, but the resulting defects await characterization. Results: The vasculature, neural tube, and cell proliferation are abnormal in the mutant. Conclusion: Brpf1 is important for embryo development and cell cycle control. Significance: This study identifies a critical role of a multivalent chromatin regulator in embryogenesis and cell proliferation.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation

You

Kou

Zou

et al. 2015

Journal of Biological Chemistry

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“…9). This thus provides some explanation about why global and conditional Brpf1 knock-out mice display severe phenotypes, including embryonic lethality at E9.5 (25,26) and abnormal forebrain development (27,28). BRPF3 Is Non-essential for Mouse Development and Survival-About the biological function of BRPF3, mouse genetic analysis indicates that it is non-essential (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Behavioral Tests-Nest-building tests were performed as described (27,36). Hind limb clasping tests were performed as reported (38).…”

Section: ␤-Gal Staining For Frozen Sections Of Brpf3mentioning

confidence: 99%

“…Although global loss of mouse Brpf1 led to embryonic lethality at E9.5, with severe defects in the vasculature and neural tube (25,26), forebrainspecific deletion caused abnormal cerebral and hippocampal development (27,28). Global inactivation of mouse Brpf2 resulted in embryonic lethality at E15.5, with growth retardation, abnormal eye development, and faulty erythropoiesis (24).…”

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The Chromatin Regulator BRPF3 Preferentially Activates the HBO1 Acetyltransferase but Is Dispensable for Mouse Development and Survival

Kou

You

Degerny

et al. 2016

Journal of Biological Chemistry

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To interpret epigenetic information, chromatin readers utilize various protein domains for recognition of DNA and histone modifications. Some readers possess multidomains for modification recognition and are thus multivalent. Bromodomain-and plant homeodomain-linked finger-containing protein 3 (BRPF3) is such a chromatin reader, containing two plant homeodomain-linked fingers, one bromodomain and a PWWP domain. However, its molecular and biological functions remain to be investigated. Here, we report that endogenous BRPF3 preferentially forms a tetrameric complex with HBO1 (also known as KAT7) and two other subunits but not with related acetyltransferases such as MOZ, MORF, TIP60, and MOF (also known as KAT6A, KAT6B, KAT5, and KAT8, respectively). We have also characterized a mutant mouse strain with a lacZ reporter inserted at the Brpf3 locus. Systematic analysis of ␤-galactosidase activity revealed dynamic spatiotemporal expression of Brpf3 during mouse embryogenesis and high expression in the adult brain and testis. Brpf3 disruption, however, resulted in no obvious gross phenotypes. This is in stark contrast to Brpf1 and Brpf2, whose loss causes lethality at E9.5 and E15.5, respectively. In Brpf3-null mice and embryonic fibroblasts, RT-quantitative PCR uncovered no changes in levels of Brpf1 and Brpf2 transcripts, confirming no compensation from them. These results indicate that BRPF3 forms a functional tetrameric complex with HBO1 but is not required for mouse development and survival, thereby distinguishing BRPF3 from its paralogs, BRPF1 and BRPF2.In the past 2 decades or so, chromatin has been gradually recognized as an important signaling platform for regulation of diverse nuclear processes, thereby forming the foundation of epigenetic phenomena (1-4). Although chromatin modifiers confer or remove covalent modifications, chromatin readers recognize such modifications through different structural modules, including the methyl CpG-binding domain, bromodomain, chromodomain, plant homeodomain-linked (PHD) 4 finger and PWWP (Pro-Trp-Trp-Pro containing) domain (5-7). Such readers are crucial for transducing signals from various cellular and environmental cues to regulate the structure and function of chromatin in the nucleus. Some chromatin readers are multivalent because they contain multiple domains for recognition of different modifications. Human BRPF3 (bromodomain-and PHD finger-containing protein 3) is one such multivalent chromatin reader, comprising two PHD fingers joined by a C2HC zinc knuckle and followed by a bromodomain and a PWWP domain (8, 9). BRPF3 is paralogous to BRPF1 and BRPF2 (10, 11). These three human proteins form a subgroup within the bromodomain superfamily, within which there are 39 other members (12, 13).Several recent studies have provided insights into the molecular and biological functions of BRPF1 and BRPF2 (11,14). The bromodomain and PWWP domain of BRPF1 bind specifically to acetylated and methylated histone H3, respectively (15-18). Along with a connecting zinc knuckle, two PHD...

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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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Deficiency of the Chromatin Regulator Brpf1 Causes Abnormal Brain Development

Cited by 50 publications

References 84 publications

The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation

The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation

The Chromatin Regulator BRPF3 Preferentially Activates the HBO1 Acetyltransferase but Is Dispensable for Mouse Development and Survival

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

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