Chromatin and transcription

Fig. 1.42A. Schematic diagram of potential linkages between chromatin and transcription.

The figure shows a simplified representation of some of the linkages between chromatin and transcription proposed on the basis of experimental evidence (Kadonaga, 1998). ... 

Prioleau, M.-N., Huet, J., Sentenac, A., and Mdchali, M. (1994). Competition between chromatin and transcription complex assembly regulates gene expression during early development. Cell 77 439-449. 

It is becoming increasingly evident that multiple linkages exist between transcription and chromatin. A large part of the function of transcription factors is dependent on and directed to the structure of chromatin. Multiple linkages exist between chromatin and transcription. Within this network, interactions between transcriptional... 

Lin R, Cook RG, Allis CD. Proteolytic removal of core histone amino termini and dephosphorylation of histone HI correlate with the formation of condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development. Gene Dev 1991 9 1601-1610. 

In a recent study, SYTOX-dyes and fluorescently-tagged proteins were used in a FRET-FLIM study to monitor DNA-protein interactions in single cells. As a control, strong FRET was monitored between GFP-labeled histon2B and SYTOX-orange. Also FRET could be detected between SYTOX (labeling chromatin) and transcriptional activator proteins [92]. 

Proteins that bind DNA at specific DNA sequences often distal from transcriptional start sites of genes. Their binding and activity is usually cell type or stimulus triggered, which subsequently decondensate the chromatin and finally lead to the recruitment of general transcription factors and the RNA polymerase. 

Coactivators enhancing the transcriptional activity of steroid hormone receptors activators include SRC-1 (steroid-receptor co-activator 1) or TEF2 (transcriptional intermediary factor 2), which are recruited by the DNA/ steroid hormone receptor complex. Their main role is to attract other transcriptional coactivators with histone acetyltransferase activity in order to decondense chromatin and allow for the binding of components of the general transcription apparatus. 

Beside coactivators so-called corepressors exist that are bound to transcription factors such as nuclear receptors and inhibit the initiation of transcription. These factors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), which interact with nuclear receptors and serve as platforms for complexes containing histone deacetylases (HDACs). These enzymes cause the reversal of histone acetylation of histones leading to a tightening of chromatin and enhancing its inaccessibility for RNA polymerase containing complexes. 

Narlikar GJ et al Cooperation between complexes that regulate chromatin structure and transcription. Cell 2002 108 475. 

Chromatin remodeling, transcription factor modification by various enzyme activities, and the communication between the nuclear receptors and the basal transcription apparatus are accomplished by protein-protein interactions with one or more of a class of coregulator molecules. The number of these coregulator molecules now exceeds 100, not counting species variations and splice variants. The first of these to be described was the CREB-binding protein, CBP. CBP, through an amino terminal domain, binds to phosphorylated serine 137 of CREB and mediates transactivation in response to cAMP. It thus is described as a coactivator. CBP and... 

Grunstein M Histone acetylation in chromatin structure and transcription. Nature 1997 389 349. 

The structure of the chromatin and their state of acetylation are important at the moment of initiating the gene transcription. Indeed, some of the transcription factors recruited by the receptor dimer have histone-acetyltransferase activity that permits the gene transcription after diminishing the condensation of the chromatin (Gruber et al. 2002 Nilsson et al. 2001 Vigushin et al. 2002). 

PHD Zn-finger (smart00249) YCSVCGKPDDGGELL QCDGCDRWYHQTCL GPPLLIEEPDGKWYCP KCK Found in nuclear proteins and implicated in chromatin-mediated transcriptional regulation. Tifl-a (NP 003843) 43... 

Regulating mono-ubiquitination of proteins by DUBs is important in histone modification where ubiquitination is thought to modulate chromatin structure and transcriptional activity. Normally, about 10% of the histone core octomers contain ubiquitinated histones and the ubiquitin is removed at mitosis by DUB activity. UBP8 has been demonstrated to regulate the ubiquitination of histone H2B, which is important in transcriptional activation of many genes [88]. 

REGULATION OF CHROMATIN STRUCTURE AND CHROMATIN-DEPENDENT TRANSCRIPTION BY POLY(ADP-RIBOSE) POLYMERASE-1... 

The Role of PARP-1 as a Specific Nucleosome-Binding Factor Effects on Chromatin Compaction and Chromatin-dependent Transcription... 

As expected, in vitro transcription assays involving PARP-1, NAD, and PARC illustrate these predicted outcomes (Kim et al, 2004). Even when driven by a transcriptional activator, such as estradiol-bound estrogen receptor, transcription is repressed when PARP-1 is added to chromatin templates. The repression is reversed by NAD+, and the NAD+-dependent effects are reversed by PARC (Kim et al, 2004). This system for transcriptional control shifts new importance onto the enzymes responsible for synthesis of NAD+ in the nucleus, such as nicotinamide mononucleotide adenylyltransferase-1 (Magni et al, 2004). Because NAD+ facilitates the decompaction of chromatin and the derepression of transcription, nuclear NAD+ biosynthetic enzymes may play critical roles as cofactors. 

---