RESUMO
The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster. A key feature of CHD1 is the presence of two chromodomains, which can bind to histone H3 methylated at lysine 4 and thus might serve to recruit and/or maintain CHD1 at the chromatin. Here, we describe genetic and biochemical approaches to the study of the Drosophila CHD1 chromodomains. We found that overall localization of CHD1 on polytene chromosomes does not appreciably change in chromodomain-mutant flies. In contrast, the chromodomains are important for transcription-independent activities of CHD1 during early embryonic development as well as for transcriptional regulation of several heat shock genes. However, neither CHD1 nor its chromodomains are needed for RNA polymerase II localization and H3K4 methylation but loss of CHD1 decreases transcription-induced histone eviction at the Hsp70 gene in vivo. Chromodomain mutations negatively affect the chromatin assembly activities of CHD1 in vitro, and they appear to be involved in linking the ATP-dependent motor to the chromatin assembly function of CHD1.
Assuntos
Montagem e Desmontagem da Cromatina , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila/genética , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Adenosina Trifosfatases/química , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Animais , Animais Geneticamente Modificados , Cromatina , Cromossomos/química , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Fertilidade , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Histonas/metabolismo , Metilação , Mutação , Estrutura Terciária de Proteína , RNA Polimerase II/metabolismo , Fatores de Transcrição/genética , Transcrição GênicaRESUMO
ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.
Assuntos
Trifosfato de Adenosina/metabolismo , Cromatina/metabolismo , Animais , Centrômero/metabolismo , Montagem e Desmontagem da Cromatina , Histonas/genética , Histonas/metabolismo , Humanos , Nucleossomos/metabolismoRESUMO
BACKGROUND: Biosample collections and biobank information systems have become a key enabler for medical research. Therefore it is important to identify potentially relevant ontologies to semantically enrich information related to the biobanking domain. OBJECTIVES: We present a three-stage semi-automated evaluation approach which allows identifying relevant ontologies for the biobanking domain based on competency questions. METHODS: After identifying candidate biobanking ontologies (Stage 1) and competency questions (Stage 2), a six-step lexical evaluation approach, which assesses the coverage of concepts, properties or instances defined by competency questions is suggested and described (Stage 3). RESULTS: We were able to perform a proof-of-concept evaluation of the OMIABIS ontology using our proposed three-stage approach together with a sample competency question. CONCLUSION: Our evaluation approach allows a swift evaluation of candidate ontology entities based on a search for higher hierarchy key terms that exist in comprehensive medical vocabularies in order to state the usability of specific ontologies for the biobanking domain.