Opening Chromatin

Lomvardas, Stavros; Thanos, Dimitris

doi:10.1016/s1097-2765(02)00463-x

Cited by 28 publications

(18 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Closed chromatin, on the other hand, does not necessarily impair binding of transcription factors [143]. In fact, transcription factors are able to open chromatin [99,33]. Reduced transcriptional activity is often associated with compacted "closed" nucleoid structures in Eubacteria [58].…”

Section: The Regulation Of Transcription By Chromatinmentioning

confidence: 99%

Innovation in gene regulation: The case of chromatin computation

Prohaska

Stadler

Krakauer

2010

Journal of Theoretical Biology

View full text Add to dashboard Cite

Chromatin regulation is understood to be one of the fundamental modes of gene regulation in eukaryotic cells. We argue that the basic proteins that determine the chromatin architecture constitute an evolutionary ancient layer of transcriptional regulation common to all three domains of life. We explore phylogenetically, sources of innovation in chromatin regulation, focusing on protein domains related to chromatin structure and function, demonstrating a step-wise increase of complexity in chromatin regulation. Building upon the highly conserved use of variants of chromosomal architectural proteins to distinguish chromosomal states, Eukarya secondarily acquired mechanisms for "writing" chemical modifications onto chromatin that constitute persistent signals. The acquisition of reader domains enabled decoding of these complex, signal combinations and a decoupling of the signal from immediate biochemical effects. We show how the coupling of reading and writing, which is most prevalent in crown-group Eukarya, could have converted chromatin into a powerful computational device capable of storing and processing more information than pure cis-regulatory networks.Key words: Chromatin, gene regulation, evolution Summary of Findings and Evolutionary HypothesisGene regulation in extant organisms is a complex adaptive system making use of a diversity of mechanisms to ensure that proteins and complementary macromolecular components are produced and maintained at functional levels in variable environments.In this contribution we focus on one key regulatory subsystem of the cell: chromatin regulation. We argue that chromatin functioned as general regulator of transcription in the primordial nucleus, and that a series of key molecular innovations has significantly expanded the regulatory scope of the cell. In this section we summarize the key empirical results of the paper. Sections 2 through 6 provide the empirical support for these claims. In section 7, we formulate an evolutionary Email addresses: sonja@bioinf.uni-leipzig.de (Sonja J. Prohaska), studla@bioinf.uni-leipzig.de (Peter F. Stadler), krakauer@santafe.edu (David C. Krakauer) hypothesis that seeks to explain our findings in terms of the evolution of proto-genetic regulation. We then interpret this evolutionary sequence in terms of increasing computational power by locating key stages of the evolutionary sequence within a formal model of computation. Since sections 2-6 are primarily concerned with presenting evidence, those interested in the conceptual development of the argument can focus on sections 7 and 8.Two variants of Chromosomal Architectural Proteins (ChAPs) are sufficient to define binary genomic, and potentially phenotypic, states. We show how extensions to this binary system lead to potential distinctions among an increasing number of genomic states, culminating in forms of control localized to specific sites in the genome, as illustrated for example by extant mammalian histone variants capable of differential expression and/or localization to r...

show abstract

Section: The Regulation Of Transcription By Chromatinmentioning

confidence: 99%

Innovation in gene regulation: The case of chromatin computation

Prohaska

Stadler

Krakauer

2010

Journal of Theoretical Biology

View full text Add to dashboard Cite

show abstract

“…RNA Pol II occupancy on a gene may also be regulated by nucleosome positioning and chromatin remodeling (57,58). Indeed, CIITA can interact with co-repressor complexes, Sin3A/HDAC1 proteins that deacetylate histones and cause compact chromatin structures (59).…”

Section: Both the Ad And Pst Domains Of Ciita May Be Required To Achimentioning

confidence: 99%

Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

Wang

Butticè

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Acetylation of core histones occurs at lysine residues on the N-terminal tails of the histones, thus neutralizing the positive charge of the histone tails and decreasing their affinity for DNA. Hyperacetylated chromatin is generally associated with transcription activation, whereas hypoacetylated chromatin is associated with transcription repression (3)(4)(5)(6).…”

mentioning

confidence: 99%

MTA1 Interacts with MAT1, a Cyclin-dependent Kinase-activating Kinase Complex Ring Finger Factor, and Regulates Estrogen Receptor Transactivation Functions

Talukder¹,

Mishra²,

Mandal³

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

The transcriptional activity of estrogen receptor-␣ is controlled by coregulators. MTA1 (metastasis-associated protein 1) represses estrogen receptor-␣-driven transcription by recruiting histone deacetylases (HDACs) to the estrogen response element containing target gene chromatin in breast cancer cells. Using a yeast twohybrid screen with the MTA1 C-terminal domain as bait, we identified MAT1 (mé nage á trois 1) as an MTA1-binding protein. MAT1 is an assembly/targeting factor for cyclin-dependent kinase-activating kinase (CAK), which has been shown to functionally interact with general transcriptional factor TFIIH, a known inducer of ER transactivation. We show that estrogen signaling promotes nuclear translocation of MAT1 and that MTA1 interacts with MAT1 both in vitro and in vivo. The eukaryotic genome is compacted with histone and other proteins to form chromatin, which consists of repeating units of nucleosome (1, 2). Formation of nucleosomes and higher order chromatin structures can render the DNA inaccessible to transcription factors and complexes. For transcription factors to access DNA, the repressive chromatin structure needs to be remodeled. Dynamic alterations in the chromatin structure can facilitate or suppress the access of the transcription factors to nucleosomal DNA, leading to transcriptional regulation. One way to achieve this is through alterations in chromatin remodeling factors or in the acetylation state of nucleosomal histones (3-5). Acetylation of core histones occurs at lysine residues on the N-terminal tails of the histones, thus neutralizing the positive charge of the histone tails and decreasing their affinity for DNA. Hyperacetylated chromatin is generally associated with transcription activation, whereas hypoacetylated chromatin is associated with transcription repression (3-6).A number of recent studies have raised the possibility of a close connection between HDACs 1 and cancer. Because HDACmediated deacetylation of nucleosomal histones is known to be associated with transcriptional repression of some genes, it is being proposed that the deregulation of recruitment of HDACcontaining repressor complex to specific target promoters could serve as a potential mechanism by which these enzymes contribute to tumorigenesis. For example, MTA1 (metastasis-associated protein 1) represses estrogen receptor-␣ (ER)-driven transcription by recruiting HDAC to the ER response element (ERE)-containing target gene chromatin in breast cancer cells (7). The NuRD-70 polypeptide of nucleosome remodeling/ HDAC complex is identical to that of the MTA1 (8 -11). The MTA1 gene was initially identified by differential expression in rat mammary adenocarcinoma metastatic cells, and its expression has been shown to correlate well with the metastatic potential of several human cell lines and tumors (12).To better understand the cellular functions of MTA1 in breast cancer cells, we performed a yeast two-hybrid screen to clone MTA1-interacting proteins. One of several isolates was identified as MAT1 (ménage á troi...

show abstract

Opening Chromatin

Cited by 28 publications

References 11 publications

Innovation in gene regulation: The case of chromatin computation

Innovation in gene regulation: The case of chromatin computation

Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

MTA1 Interacts with MAT1, a Cyclin-dependent Kinase-activating Kinase Complex Ring Finger Factor, and Regulates Estrogen Receptor Transactivation Functions

Contact Info

Product

Resources

About