Neural development is regulated by both external environment and internal signals, and in addition to transcription factors, epigenetic modifications also play an important role. By focusing on the genetic mechanism of ATP-dependent chromatin remodeling in children with neurodevelopmental disorders, this article elaborates on the effect of four chromatin remodeling complexes on neurogenesis and the development and maturation of neurons and neuroglial cells and introduces the clinical research advances in neurodevelopmental disorders.
Child ; Chromatin ; Chromatin Assembly and Disassembly ; Humans ; Neurodevelopmental Disorders/genetics* ; Neurogenesis ; Transcription Factors/genetics*

The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.
Chromatin/genetics* ; Chromatin Assembly and Disassembly ; Gene Regulatory Networks ; Humans ; Psoriasis/genetics* ; T-Lymphocytes, Regulatory

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.
Mice ; Animals ; Memory ; Chromatin Assembly and Disassembly ; Hippocampus/metabolism* ; Transcription Factors/metabolism* ; Chromatin/metabolism* ; Metabolic Networks and Pathways

Prostate cancer is one of the most common diseases in men worldwide. Surgery, radiation therapy, and hormonal therapy are effective treatments for early-stage prostate cancer. However, the development of castration-resistant prostate cancer has increased the mortality rate of prostate cancer. To develop novel drugs for castration-resistant prostate cancer, the molecular mechanisms of prostate cancer progression must be elucidated. Among the signaling pathways regulating prostate cancer development, recent studies have revealed the importance of noncanonical wingless-type MMTV integration site family (WNT) signaling pathways, mainly that involving WNT5A, in prostate cancer progression and metastasis; however, its role remains controversial. Moreover, chromatin remodelers such as the switch/sucrose nonfermentable (SWI/SNF) complex and chromodomain helicase DNA-binding proteins 1 also play important roles in prostate cancer progression through genome-wide gene expression changes. Here, we review the roles of noncanonical WNT signaling pathways, chromatin remodelers, and epigenetic enzymes in the development and progression of prostate cancer.
Male ; Humans ; Wnt Signaling Pathway ; Chromatin ; Prostatic Neoplasms, Castration-Resistant ; Chromatin Assembly and Disassembly

In the post-genomic era, the mechanisms controlling activation of genes are thought to be more important. Gene-environment interactions are crucial in both development and treatment of psychiatric disorders as they are complex genetic disorders. Epigenetics is defined as a change of gene expression that occurs without a change of DNA sequence and can be heritable by certain mechanisms. Epigenetic changes play essential roles in control of gene activation. DNA methylation, chromatin remodeling and RNAi act as key mechanisms for epigenetic modifications of genes. Here, we review the basic mechanisms of epigenetics and discuss their potential involvement of human diseases, including psychiatric disorders.
Base Sequence ; Chromatin Assembly and Disassembly ; DNA Methylation ; Epigenomics ; Gene Expression ; Gene-Environment Interaction ; Humans ; Transcriptional Activation

Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWI/SNF chromatin-remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological signals. The ATP-dependent SWI/SNF chromatin-remodeling complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different metabolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.
Chromatin Assembly and Disassembly ; DNA-Binding Proteins ; metabolism ; Disease ; Humans ; Metabolism ; Nutrients ; metabolism ; Signal Transduction

Autism spectrum disorder (ASD) is a series of neurodevelopmental disorder with a large genetic component. However, the pathogenic genes and molecular mechanisms of ASD have not been clearly defined. Recent technological advancements, such as next-generation sequencing, have led to the identification of certain loci that is responsible for the pathophysiology of ASD. Three functional pathways, such as chromatin remodeling, Wnt signaling and mitochondrial dysfunction are potentially involved in ASD. In this review, we will focus on recent studies of the involvement of Wnt signaling pathway components in ASD pathophysiology and related drugs used in ASD treatment.
Autism Spectrum Disorder* ; Autistic Disorder* ; beta Catenin ; Chromatin Assembly and Disassembly ; Neurodevelopmental Disorders ; Wnt Signaling Pathway*

Long non-coding RNAs (lncRNAs) are a group of endogenous RNA molecules which exceed 200 nt in length, lack complete specific open reading frame, and completely lack or possessvery limited protein-coding capacity. Recent studies have revealed that lncRNAs participate in critical processes such as genomic imprinting, cell differentiation, and immune reaction, etc. lncRNAs regulate gene expression at the epigenetic, transcriptional and post-transcriptional levels by modulating chromatin remodeling and histone modifications, interfering the transcription, regulating patterns of alternative splicing, generating small RNAs, and modulating protein activation and localization. Through their numerous functions, lncRNAs play critical roles in the growth, development, senescence, death, and other important physiological and pathological processes. Further investigation into the regulation of gene expression mediated by lncRNAs will be of great value in the thorough understanding of pathogenies and provide new molecular markers and drug targets of diseases.
Alternative Splicing ; Chromatin Assembly and Disassembly ; Gene Expression ; Open Reading Frames ; Proteins ; RNA, Long Noncoding

Eukaryotic DNA is hierarchically packaged into chromatin to fit inside the nucleus. Dynamics of the chromatin structure plays a critical role in transcriptional regulation and other biological processes that involve DNA, such as DNA replication and DNA repair. Many factors, including histone variants, histone modification, DNA methylation and the binding of non-histone architectural proteins regulate the structure of chromatin. Although the structure of nucleosomes, the fundamental repeating unit of chromatin, is clear, there is still much discussion on the higher-order levels of chromatin structure. Identifying the structural details and dynamics of higher-order chromatin fibers is therefore very important for understanding the organization and regulation of gene activities. Here, we review studies on the dynamics of chromatin higher order structure and its relationship with gene transcription.
Animals ; Chromatin ; chemistry ; metabolism ; Chromatin Assembly and Disassembly ; Eukaryotic Cells ; chemistry ; metabolism ; Gene Expression Regulation ; Humans ; Models, Molecular

OBJECTIVEA CAT reporter plasmid (pBLCAT3alpha1) driven by the promoter of hsp90alpha was in vitro assembled into chromatin to investigate the transcription activity of the reporter gene upon heat shock.

METHODSA competitive RT-PCR-based technique was used to quantify the promoter activity of hsp90alpha gene on chromatin or naked DNA templates in vitro.

RESULTSThe in vitro transcription efficiency was first optimized by using different amounts of whole cell extracts from heat shock-treated HeLa cells. In vitro chromatin assembly was carried out with purified components of chromatin assembly associated factors, core histones and CAT reporter gene driven by the promoter of hsp90alpha gene. Results showed that chromatin formation repressed the in vitro transcription of the gene.

CONCLUSIONThe heat shock induced transcription of hsp90alpha gene on chromatin template is more efficient than that on naked DNA in vitro.

Chromatin Assembly and Disassembly ; genetics ; Genes, Reporter ; genetics ; HSP90 Heat-Shock Proteins ; genetics ; Heat-Shock Response ; genetics ; Humans ; Transcription, Genetic