A Proline-Rich Region in the Zeste Protein Essential for Transvection and white Repression by Zeste1

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1865-1874
Author(s):  
Christina Rosen ◽  
Dale Dorsett ◽  
Joseph Jack

Abstract The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. We characterized two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, we suggest that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the maintenance complexes.

1993 ◽  
Vol 13 (11) ◽  
pp. 6810-6818 ◽  
Author(s):  
X Y Zhang ◽  
N Jabrane-Ferrat ◽  
C K Asiedu ◽  
S Samac ◽  
B M Peterlin ◽  
...  

A mammalian protein called RFX or NF-X binds to the X box (or X1 box) in the promoters of a number of major histocompatibility (MHC) class II genes. In this study, RFX was shown to have the same DNA-binding specificity as methylated DNA-binding protein (MDBP), and its own cDNA was found to contain a binding site for MDBP in the leader region. MDBP is a ubiquitous mammalian protein that binds to certain DNA sequences preferentially when they are CpG methylated and to other related sequences, like the X box, irrespective of DNA methylation. MDBP from HeLa and Raji cells formed DNA-protein complexes with X-box oligonucleotides that coelectrophoresed with those containing standard MDBP sites. Furthermore, MDBP and X-box oligonucleotides cross-competed for the formation of these DNA-protein complexes. DNA-protein complexes obtained with MDBP sites displayed the same partial supershifting with an antiserum directed to the N terminus of RFX seen for complexes containing an X-box oligonucleotide. Also, the in vitro-transcribed-translated product of a recombinant RFX cDNA bound specifically to MDBP ligands and displayed the DNA methylation-dependent binding of MDBP. RFX therefore contains MDBP activity and thereby also EF-C, EP, and MIF activities that are indistinguishable from MDBP and that bind to methylation-independent sites in the transcriptional enhancers of polyomavirus and hepatitis B virus and to an intron of c-myc.


2020 ◽  
Author(s):  
Manthan Patel ◽  
Divyesh Patel ◽  
Subhamoy Datta ◽  
Umashankar Singh

ABSTRACTThe antineoplastic agent Givinostat inhibits histone deacetylases. We present here our finding that the DNA-binding of human CGGBP1 is also inhibited by Givinostat. CGGBP1, a DNA-binding protein, is required for cancer cell proliferation. In our quest to exploit the potential anti-proliferative effects of CGGBP1 inhibition, we have developed a simple screening assay to identify chemical inhibitors of DNA-protein interactions. We have applied this screen for human CGGBP1 on a library of 1685 compounds and found that Givinostat is a direct inhibitor of CGGBP1-DNA interaction. The mechanism of action of Givinostat should thus extend beyond HDACs to include the inhibition of the myriad functions of CGGBP1 that depend on its binding to the DNA.


Author(s):  
Emmanuel Prikas ◽  
Holly Ahel ◽  
Kristie Stefanoska ◽  
Prita Riana Asih ◽  
Alexander Volkerling ◽  
...  

The microtubule-associated protein tau is a key factor in neurodegenerative proteinopathies and is predominantly found in the neuronal axon. However, somatodendritic localization of tau occurs for a subset of pathological and physiologic tau. Dendritic tau can localize to post-synapses where it interacts with proteins of the post-synaptic density (PSD) protein PSD-95, a membrane-associated guanylate kinase (MAGUK) scaffold factor for organization of protein complexes within the PSD, to mediate downstream signals. The sub-molecular details of this interaction, however, remain unclear. Here, we use interaction mapping in cultured cells to demonstrate that tau interacts with the guanylate kinase (GUK) domain in the C-terminal region of PSD-95. The PSD-95 GUK domain is required and sufficient for a complex with full-length human tau. Mapping the interaction of the MAGUK core on tau revealed the microtubule binding repeats 2 and 3 and the proline-rich region contribute to this interaction, while the N- and C-terminal regions of tau inhibit interaction. These results reveal intramolecular determinants of the protein complex of tau and PSD-95 and increase our understanding of tau interactions regulating neurotoxic signaling at the molecular level.


2012 ◽  
Vol 287 (10) ◽  
pp. 7512-7525 ◽  
Author(s):  
Mauricio Budini ◽  
Emanuele Buratti ◽  
Cristiana Stuani ◽  
Corrado Guarnaccia ◽  
Valentina Romano ◽  
...  

2015 ◽  
Vol 51 (39) ◽  
pp. 8381-8384 ◽  
Author(s):  
Zheng-Yuan Ma ◽  
Yi-Fan Ruan ◽  
Nan Zhang ◽  
Wei-Wei Zhao ◽  
Jing-Juan Xu ◽  
...  

A novel photoelectrochemical approach was achieved for the detection of a DNA binding protein via the protein–DNA interaction.


2007 ◽  
Vol 27 (17) ◽  
pp. 6243-6253 ◽  
Author(s):  
Gang Yao ◽  
Yueh-Chin Chiang ◽  
Chongxu Zhang ◽  
Darren J. Lee ◽  
Thomas M. Laue ◽  
...  

ABSTRACT The mRNA deadenylation process, catalyzed by the CCR4 deadenylase, is known to be the major factor controlling mRNA decay rates in Saccharomyces cerevisiae. We have identified the proline-rich region and RRM1 domains of poly(A) binding protein (PAB1) as necessary for CCR4 deadenylation. Deletion of either of these regions but not other regions of PAB1 significantly reduced PAB1-PAB1 protein interactions, suggesting that PAB1 oligomerization is a required step for deadenylation. Moreover, defects in these two regions inhibited the formation of a novel, circular monomeric PAB1 species that forms in the absence of poly(A). Removal of the PAB1 RRM3 domain, which promoted PAB1 oligomerization and circularization, correspondingly accelerated CCR4 deadenylation. Circular PAB1 was unable to bind poly(A), and PAB1 multimers were severely deficient or unable to bind poly(A), implicating the PAB1 RNA binding surface as critical in making contacts that allow PAB1 self-association. These results support the model that the control of CCR4 deadenylation in vivo occurs in part through the removal of PAB1 from the poly(A) tail following its self-association into multimers and/or a circular species. Known alterations in the P domains of different PAB proteins and factors and conditions that affect PAB1 self-association would, therefore, be expected to be critical to controlling mRNA turnover in the cell.


2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicholas W. Ashton ◽  
Dorothy Loo ◽  
Nicolas Paquet ◽  
Kenneth J. O’Byrne ◽  
Derek J. Richard

Sign in / Sign up

Export Citation Format

Share Document