OBJECTIVETo investigate the expression and amplification of steroid receptor coactivator- 3(SRC- 3) gene in colorectal carcinoma (CRC) and its clinicopathological significance.

METHODSImmunohistochemistry and fluorescence in situ hybridization (FISH) were used to detect the expression and amplification of SRC- 3 gene in CRC, and its association with patient's clinical pathological features was analyzed.

RESULTSA total of 60 patients with CRC were studied. SAR- 3 proteins were overexpressed in 23 cases (38% ). There was a significant association between SAR- 3 overexpression and neoplasm staging (P< 0.01). SRC- 3 protein was overexpressed in 62% of patients with Dukes C or D stage, whereas SRC- 3 protein was normally expressed in 74% of patients with Dukes A or B stage. As for FISH study, 47 cases were informative. High- level amplification of SRC- 3 gene was detected in 6 cases(13% ) and all showed overexpression of SRC- 3 protein. Low- level amplification of SRC- 3 was observed in 9 cases (19% ). Overexpression of SRC- 3 was detected in 6 cases. The remaining 9 of 32 patients(28% ) without amplification of SRC- 3 gene were observed with overexpression of SRC- 3 protein. In addition, 91% patients with CRC were found overexpression of SRC- 3 as well as overexpression of P53.

CONCLUSIONThe abnormal expression of SRC- 3 gene might impact on the function of P53 and development of CRC. There might exist some unknown mechanisms other than gene amplification of SRC- 3 to regulate its encoded protein expression in CRC.

Biomarkers, Tumor ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Gene Expression ; Histone Acetyltransferases ; genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Nuclear Receptor Coactivator 3 ; Trans-Activators ; genetics

OBJECTIVETo investigate the role of AIB1 gene in the development of esophageal squamous cell carcinoma (ESCC) and its clinicopathologic significance.

METHODSTwo tissue microarrays, including 203 cases of ESCC, were prepared. Fluorescence in-situ hybridization (FISH) and immunohistochemistry were performed to detect the amplification of AIB1 gene and expression of its encoded protein in ESCC. The results were correlated with various clinicopathologic parameters.

RESULTSIn the 203 cases of ESCC studied, FISH was successful in 115 cases. Amongst those, amplification/gain of AIB1 gene was observed in 15 cases, including high-level amplification in 5 cases (4.3%) and low-level gain in 10 cases (8.7%). As for immunohistochemical study, AIB1 protein was overexpressed in 94 cases of ESCC. There was a significant association of AIB1 overexpression and tumor staging. AIB1 was overexpressed in 66 of the 123 cases in advanced T stages (T3 to 4), compared with 25 of the 80 cases in early T stages (P = 0.008). Those cases with high-level amplification of AIB1 also showed overexpression of its encoded protein. On the other hand, 8 of the 10 cases with low-level gain of AIB1 showed protein overexpression. The remaining 41 of the 100 cases which did not have AIB1 gene amplification/gain demonstrated overexpression of AIB1 protein.

CONCLUSIONOverexpression of AIB1 protein caused by gene amplification/gain or other molecular mechanisms may play an important role in the development and/or progression of a subset of ESCC.

Carcinoma, Squamous Cell ; genetics ; pathology ; Cell Movement ; genetics ; Disease Progression ; Esophageal Neoplasms ; genetics ; pathology ; Female ; Gene Amplification ; Histone Acetyltransferases ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; methods ; Lymphatic Metastasis ; pathology ; Male ; Neoplasm Staging ; Nuclear Receptor Coactivator 3 ; genetics ; metabolism ; Tumor Cells, Cultured

The aim of this study was to obtain the soluble protein of human pregnane X receptor ligand binding domain (PXRLBD) through the coexpression of PXRLBD and 88 amino acids of steroid receptor coactivator-1 (SRC88) and apply the protein to constructing a new model of screening PXR ligands. Expression plasmid of pETDuet-1-SRC88-PXRLBD was constructed and transformed into Escherichia coli Rosetta (DE3) to coexpress PXRLBD and SRC88 via induction by IPTG at low temperature. Then an equilibrium dialysis model was constructed to study the interaction between PXRLBD and drugs including clotrimazole and dexamethasone, using HPLC as the analysis method. The results showed that the soluble protein of PXRLBD was obtained and the HPLC data indicated that clotrimazole bound to PXRLBD, while dexamethasone did not bind to PXRLBD, which indicated the successful establishment of a new method for studying the interaction between PXR and drugs. The new method may be useful in the screening of PXR ligands in vitro.
Clotrimazole ; metabolism ; Dexamethasone ; metabolism ; Dialysis ; methods ; Drug Interactions ; Escherichia coli ; genetics ; metabolism ; Histone Acetyltransferases ; genetics ; metabolism ; Humans ; Ligands ; Nuclear Receptor Coactivator 1 ; Plasmids ; Protein Binding ; Receptors, Steroid ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Transformation, Genetic

OBJECTIVE: To analyze the genotype and clinical phenotype of a 3-month-old female infant featuring unresponsiveness. METHODS: The infant was subjected to genetic testing, and her clinical features were compared with syndromes associated with variants of the candidate gene. RESULTS: The patient has featured long fingers, long and overlapped toes, musk-like face, blepharophimosis, ptosis, and lacrimal duct anomaly. She was found to harbor a heterozygous de novo variant NM_012330.3: c.3040C>T (p.Gln1014*) in exon 16 of the KAT6B gene. Her clinical phenotype and genotype have both conformed to Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS). CONCLUSION The child was diagnosed with SBBYSS syndrome due to the c.3040C>T (p.Gln1014*) variant of the the KAT6B gene. Discovery of the unique features has expanded the phenotypic spectrum of this syndrome.
Female ; Humans ; Blepharophimosis/genetics* ; Blepharoptosis ; Genotype ; Histone Acetyltransferases ; Infant

Histone acetylation is one of the epigenetic modifications. Histone acetylation, which is catalyzed by histone acetyltransferases and negatively regulated by histone deacetylases, plays an important role in a variety of cellular physiological and pathophysiological processes. Recent studies have shown that histone deacetylases are involved in a variety of pathophysiological responses to acute kidney injury, such as apoptosis, dedifferentiation, proliferation and regeneration. This article reviews the role and underlying mechanism of histone deacetylases in acute kidney injury induced by ischemia reperfusion, nephrotoxicants, sepsis and rhabdomyolysis.
Acetylation ; Acute Kidney Injury ; Histone Acetyltransferases/metabolism* ; Histone Deacetylases/metabolism* ; Humans ; Protein Processing, Post-Translational

Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation. Despite their important functions in deacetylation, no strong effects on global gene expression have been seen under optimized or laboratory growth conditions. Instead, H3K4me2-Set3 HDAC and Set2-Rpd3S pathways primarily delay the kinetics of messenger RNA (mRNA) and long noncoding RNA (lncRNA) induction upon environmental changes. A majority of mRNA genes regulated by these pathways have an overlapping lncRNA transcription either from an upstream or an antisense promoter. Surprisingly, the distance between mRNA and lncRNA promoters seems to specify the repressive effects of the two pathways. Given that co-transcriptional methylations and acetylation have been linked to many cancers, studying their functions in a dynamic condition or during cancer progression will be much more important and help identify novel genes associated with cancers.
Acetylation ; Gene Expression* ; Histone Acetyltransferases ; Histone Deacetylases ; Histones* ; Humans ; Kinetics ; Methylation* ; RNA, Long Noncoding ; RNA, Messenger ; Yeasts

Diagnostic exome sequencing (DES) is a powerful tool to analyze the pathogenic variants leading to development delay (DD) and intellectual disability (ID). Recently, heterozygous de novo mutation of the histone acetyltransferase encoding gene KAT6B has been recognized as causing a syndrome with congenital anomalies and intellectual disability, namely Say-Barber-Biesecker-Young-Simpson (SBBYS) syndrome. Here we report a case of SBBYS syndrome in a third generation Korean family affected with a missense mutation in KAT6B, c.2292C>T p.(His767Tyr) identified by DES. This is the first confirmed familial inherited mutation of the KAT6B reported worldwide. Our case emphasizes again the importance of basic physical examination and taking a family history. Furthermore, advances in genetic diagnostic tools are becoming key to identifying the etiology of DD and ID. This allows a physiatrist to predict the disease's clinical evolution with relative certainty, and offer an appropriate rehabilitation plan for patients.
Exome* ; Family Characteristics* ; Histone Acetyltransferases ; Humans ; Intellectual Disability ; Mutation, Missense ; Physical Examination ; Rehabilitation

OBJECTIVE: To study the interactive regulatory effect of histone acetylation and methylation on cardiomyogenesis, and to provide a theoretical basis for the prevention and treatment of congenital heart disease. METHODS: A total of 24 Kunming mice were randomly divided into embryo day 14.5 (ED 14.5) group, embryo day 16.5 (ED 16.5) group, postnatal day 0.5 (PND 0.5) group, and postnatal day 7 (PND 7) group, with 6 mice in each group, and the heart tissue of fetal and neonatal mice was collected. Colorimetry was used to measure the activities of histone acetylases (HATs) and histone methyltransferases (HMTs) in the myocardium. Western blot was used to measure the expression of H3K9ac and H3K9me3 in the myocardium. RESULTS: Colorimetry showed that the activities of HATs and HMTs were higher before birth and were lower after birth. There was a significant difference in the activity of HATs in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 group (P<0.05), as well as between the PND 7 group and the ED 16.5 group (P<0.05). There was also a significant difference in the activity of HMTs in the myocardium between the PND 7 group and the ED 14.5 and ED 16.5 groups (P<0.05). Western blot showed higher expression of H3K9ac and H3K9me3 before birth and lower expression of H3K9ac and H3K9me3 after birth, and there were significant differences in the expression H3K9ac and H3K9me3 in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 and ED 16.5 groups (P<0.05). CONCLUSIONS The dynamic expression of HATs, HMTs, H3K9ac, and H3K9me3 is observed during cardiomyogenesis, suggesting that histone H3K9ac acetylation and histone H3K9me3 methylation mediated by HATs and HMTs may play a role in interactive regulation during cardiomyogenesis.
Acetylation ; Animals ; Histone Acetyltransferases ; Histones ; metabolism ; Methylation ; Mice ; Protein Processing, Post-Translational

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation and speech delay. METHODS: Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy. RESULTS: The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c.56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c.5314dupA variant of the KAT6A gene in the fetus. CONCLUSION The heterozygous c.5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.
Child ; Humans ; Male ; Pregnancy ; Histone Acetyltransferases ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree

BACKGROUND: It has generally been proven that histone acetylation and deacetylation are involved in the malignant transformation. To date, however, this has rarely been studied in cases of malignant lymphoma. METHODS: We studied nine cases of reactive lymphoid hyperplasia, 78 cases of diffuse large B-cell lymphoma (DLBCL), 13 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 cases of extranodal NK/T-cell lymphoma, nasal type (NKTCL). Thus, we attempted to elucidate the associations of the degree of the expression of histone acetyltransferase 1 (HAT1), histone deacetylase (HDAC) 1, HDAC2, and HDAC3 with the clinical behaviors of above malignant lymphomas using the immunohistochemistry and a western blot analysis. RESULTS: The degree of the expression of HAT1 was higher in cases of DLBCL, PTCL-NOS or NKTCL as compared with reactive lymphoid hyperplasia (p<0.05). The degree of the expression of HAT1 was correlated with that of HDAC1 in cases of DLBCL or NKTCL (p<0.05). The degree of the expression of HAT1 and HDAC1 was correlated with a poor survival in cases of DLBCL or PTCL-NOS (p>0.05). CONCLUSIONS: HAT1, HDAC1, and HDAC2 play a critical role in the development of malignant lymphomas. Both HAT1 and HDAC1 might be indicators for a poor prognosis in cases of DLBCL as cooperating factors.
Acetylation ; B-Lymphocytes ; Blotting, Western ; Histone Acetyltransferases ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; Histones ; Immunohistochemistry ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, T-Cell, Peripheral ; Prognosis ; Pseudolymphoma