How May Chromatin Remodeling Affect Transcription?

Chromatin-remodeling is a process that involves the modification of chromatin architecture to allow access to condensed genomic DNA to the regulatory transcription machinery proteins. This process can be regulated through various mechanisms, including histone modification, chromatin remodeling, histone variant incorporation, and histone eviction. Chromatin remodeling complexes (CRCs) use ATP energy to disrupt nucleosome DNA contacts, move nucleosomes along DNA, and remove.

Histone-modifying and remodeling complexes are considered the main coregulators that affect transcription by changing the chromatin structure. Histone modification can open chromatin, allowing selective binding of transcription factors that, in turn, recruit RNA polymerase II. As chromatin is condensed into the primary nucleosome structure, DNA becomes less accessible for transcription factors. With the loosening of chromatin, specific DNA-binding transcription factors recruit histone acetylases and deacetylases to promoters to activate or repress transcription.

Chromatin remodeling ultimately results in altered accessibility of transcription factors to regulatory DNA. Understanding how chromatin remodeling is detected is crucial for understanding the role of epigenetic modifications to histone proteins in modifying the structure of chromatin resulting in transcriptional activation or repression. Chromatin structure imposes significant obstacles on all aspects of transcription mediated by RNA polymerase II.

Dynamic changes in chromatin conformation alter the organization and structure of the genome and further regulate gene transcription. In particular, chromatin remodeling can dynamically regulate gene expression by altering accessibility of chromatin to transcription factors. The scope of chromatin remodeling is vast, with its role in gene expression being a key focus in understanding the regulation of gene expression.

What is the function of the chromatin remodeling?

Chromatin remodeling plays a crucial role in cell growth and division, allowing tumor-suppressor function. Mutations in chromatin remodelers and deregulated covalent histone modifications can favor self-sufficiency in cell growth and escape from growth-regulatory cell signals, which are hallmarks of cancer. Inactivating mutations in SMARCB1, formerly known as hSNF5/INI1, have been found in rhabdoid tumors, affecting the pediatric population. Similar mutations are also present in other childhood cancers, such as choroid plexus carcinoma, medulloblastoma, and some acute leukemias.

Several subunits of the human SWI/SNF chromatin remodeling complex have been found mutated in various neoplasms since the original observation of SMARCB1 mutations in rhabdoid tumors. The SWI/SNF ATPase BRG1 (or SMARCA4) is the most frequently mutated chromatin remodeling ATPase in cancer, with mutations showing an unusually high preference for missense mutations that target the ATPase domain. These mutations are enriched at highly conserved ATPase sequences, acting genetically dominantly to alter chromatin regulatory function at enhancers and promoters.

Inactivating mutations in BCL7A in Diffuse large B-cell lymphoma (DLBCL) and other haematological malignancies, PML-RARA fusion protein in acute myeloid leukemia recruits histone deacetylases, leading to repression of genes responsible for myelocyte differentiation, leading to leukemia. Tumor suppressor Rb protein functions by recruiting human homologs of the SWI/SNF enzymes BRG1, histone deacetylase, and DNA methyltransferase. Mutations in BRG1 are reported in several cancers causing loss of tumor suppressor action of Rb.

Recent reports indicate DNA hypermethylation in the promoter region of major tumor suppressor genes in several cancers, mainly in colorectal and breast cancers. Histone Acetyl Transferases (HAT) p300 mutations are most commonly reported in colorectal, pancreatic, breast, and gastric carcinomas. HATs have diverse roles as transcription factors, including hADA3 acting as an adaptor protein linking transcription factors with other HAT complexes.

What is the role of chromatin in the alterations of gene expression?

Gene expression in eukaryotes is regulated at multiple levels, including transcriptional, cis-regulatory, and epigenetic factors. DNA methylation and histone modifications play crucial roles in epigenetic regulation of genes. Understanding the structural properties and spatial organization of chromatin at the 3-D level is crucial for evaluating gene expression regulation. Dynamic alternations of chromatin conformation can either activate gene expression by facilitating interactions between enhancers or other cis-regulatory elements and their target genes, or suppress gene expression by blocking interactions due to steric hindrance.

Although the exact molecular mechanisms underlying gene regulation via conformational changes of chromatin remain unclear, epigenetic studies, including histone modification, nucleosome positioning, chromosome territories, and chromatin interactions, have provided evidence to demonstrate the significance of chromatin conformation in eukaryotic gene regulation. Recent advances on dynamic alterations of chromatin in gene regulation occur at different levels from primary structure to three-dimensional conformation.

How does chromatin structure regulate transcription in eukaryotes?

The chromatin structure is a key regulator of gene transcription. Genes with more open or relaxed chromatin are more accessible for this process, which is a fundamental regulatory point for numerous genes.

How can chromatin structure be altered?

The structure of higher-order chromatin can be altered by modifications, such as acetylation, which neutralizes the basic charge of lysine. This modification has the most potential to unfold chromatin, as it affects the interaction between different histones in adjacent nucleosomes or histones with DNA. This information is sourced from ScienceDirect, a website that uses cookies and holds copyright for text and data mining, AI training, and similar technologies.

How modifications to chromatin can affect transcriptional activity?

Chromatin modifications can impact transcriptional activity by altering the accessibility of DNA to the transcription machinery. There are various processes that may or may not cause chromatin remodeling, and each description can be matched to its effect on transcriptional activity. The provided descriptions are examples of various processes that may or may not cause chromatin remodeling. Matching each description to its effect on transcriptional activity is crucial for understanding the relationship between chromatin modifications and the transcription machinery. The question is asking for a detailed solution from a subject matter expert to help students learn core concepts related to chromatin modifications.

How do chromatin modifications regulate transcription?

This review discusses the study of histone-modifying and remodeling complexes, which are the main coregulators that affect transcription by changing chromatin structure. Coordinated action by these complexes is essential for the transcriptional activation of any eukaryotic gene. The review covers the functional impact of transcriptional proteins/complexes, remodeling and modification of non-histone proteins by transcriptional complexes, the supplementary functions of non-catalytic subunits of remodelers, and the participation of histone modifiers in the “pause” of RNA polymeraseII. It also includes a scheme illustrating the recruitment of the main classes of remodelers and chromatin modifiers to various sites in the genome and their functional activities.

How does chromatin remodeling affect transcription?

Chromatin structure changes due to its condensation, making DNA less accessible for transcription factors. However, with loosening the chromatin structure, transcription machinery can access genomic DNA, promoting transcription. Nucleosome organization and dynamics are regularly modified by covalent post-translational modifications (PTMs), histone chaperones, ATP-dependent nucleosome remodelers, and histone variants.

Common local changes include replacing an octamer via ATP-dependent chromatin-remodeling enzymes, stabilizing or destabilizing the chromatin via methylation and acetaylation, and repositioning nucleosomal DNA to enable the binding of a regulatory factor.

Over 100 distinct posttranslational modifications (PTMs) of histone have been described, often occurring at the N-terminal of histone tails. Some trends have been identified: acetylation, phosphorylation, and ADP-ribosylation weaken charge-dependent interactions between histones and DNA, increasing genetic material accessibility to transcription machinery. Lysine methylation increases nucleosomal stability and promotes heterochromatin formation, reducing DNA accessibility.

Histone formation is dynamic, and the rate of histone turnover can occur rapidly. It has been proposed that mechanisms exist to maintain specific PTMs even in the face of ongoing nucleosome turnover and DNA replication. Some histone-modifying enzymes, such as HDACs, methyltransferases Suv39h, SETDB1, SetD8, and G9a, remain associated with chromatin during its turnover, allowing them to modify their cognate residues immediately following the deposition of new histones.

How do chromatin remodeling complexes alter the structure of DNA?

The complexes consist of multiple reader domains and a catalytic domain that uses ATP hydrolysis energy to disrupt boundaries between histone proteins and DNA. This leads to changes in nucleosome conformation, increasing DNA accessibility. The site uses cookies and is copyrighted by Elsevier B. V., its licensors, and contributors. All rights reserved for text and data mining, AI training, and similar technologies. Creative Commons licensing terms apply for open access content.

What is the function of the chromatin remodelers?

Chromatin remodelers are essential for regulating cellular processes like transcription and DNA repair by controlling access to genomic DNA. Four families of chromatin remodelers have been identified in yeast, each playing non-redundant roles within the cell. These remodelers regulate multiple cellular processes, including AI training and text and data mining. All rights reserved, including those for text and data mining.

What is the mechanism of action of chromatin remodeling complexes?

The RSC chromatin-remodeling complex, as studied biochemically and structurally, is proposed to release DNA from the histone surface, initiate DNA translocation, and complete the remodeling process through ATP binding.

What is the role of chromatin in transcription?

The chromatin structure, which is regulated through a variety of mechanisms, including histone modification, chromatin remodeling, histone variant incorporation, and histone eviction, has a significant impact on transcription processes mediated by RNA polymerase II.