The artificial 4-zinc-finger protein Bagly binds human utrophin promoter A at the endogenous chromosomal site and activates transcription

2007 ◽  
Vol 85 (3) ◽  
pp. 358-365 ◽  
Author(s):  
Annalisa Onori ◽  
Agata Desantis ◽  
Serena Buontempo ◽  
Maria Grazia Di Certo ◽  
Maurizio Fanciulli ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activity ◽  
Zinc Finger Protein ◽  
Target Sequence ◽  
Zinc Finger Domain ◽  
Active Chromatin ◽  
Finger Protein ◽  
Chromosomal Site ◽  
Transcription Factor Yy1 ◽  
Test Gene

Our aim is to upregulate the expression of the dystrophin-related gene utrophin in Duchenne muscular dystrophy, in this way complementing the lack of dystrophin function. To achieve utrophin upregulation, we designed and engineered synthetic zinc-inger based transcription factors. We have previously shown that the artificial 3-zinc-finger protein Jazz, fused with the appropriate effector domain, is able to drive the transcription of a test gene from utrophin promoter A. Here we report a novel artificial 4-zinc-finger protein, Bagly, which binds with optimized affinity–specificity to a 12 bp DNA target sequence that is internal to human utrophin promoter A. Bagly was generated adding to Jazz protein an extra-fourth zinc finger, derived from transcription factor YY1. Importantly, the Bagly DNA target sequence is statistically present in the human genome only 210 times, about 60 fewer times than the 9 bp Jazz DNA target sequence. Thanks to its additional zinc-finger domain, Bagly protein shows enhanced transcriptional activity. Moreover, we demonstrated Bagly's effective access and binding to active chromatin in the chromosomal context and its ability to upregulate endogenous utrophin.

scholarly journals A SWI2/SNF2-type ATPase/helicase protein, mDomino, interacts with myeloid zinc finger protein 2A (MZF-2A) to regulate its transcriptional activity

2003 ◽  
Vol 8 (4) ◽  
pp. 325-339 ◽  
Author(s):  
Hironori Ogawa ◽  
Takeshi Ueda ◽  
Tomohisa Aoyama ◽  
Ami Aronheim ◽  
Shigekazu Nagata ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activity ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Myeloid Zinc Finger

scholarly journals The zinc finger protein CLAMP promotes long-range chromatin interactions that mediate dosage compensation of the Drosophila male X-chromosome

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
William Jordan ◽  
Erica Larschan
Keyword(s):  
Long Range ◽  
Zinc Finger ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Zinc Finger Protein ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Active Chromatin ◽  
Finger Protein

Abstract Background Drosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that expressed from the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space largely independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome. Results Here, we demonstrate that CLAMP promotes the observed three-dimensional clustering of MSLc binding sites. Moreover, the X-enriched CLAMP protein more strongly promotes longer-range three-dimensional interactions on the X-chromosome than autosomes. Genome-wide, CLAMP promotes three-dimensional interactions between active chromatin regions together with other insulator proteins. Conclusion Overall, we define how long-range interactions which are modulated by a locally enriched ubiquitous transcription factor promote hyper-activation of the X-chromosome to mediate dosage compensation.

scholarly journals ZNF552, a novel human KRAB/C2H2 zinc finger protein, inhibits AP-1- and SRE-mediated transcriptional activity

BMB Reports ◽  
2010 ◽  
Vol 43 (3) ◽  
pp. 193-198 ◽  
Author(s):  
Yun Deng ◽  
Bisheng Liu ◽  
Xiongwei Fan ◽  
Yuequn Wang ◽  
Ming Tang ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activity ◽  
Zinc Finger Protein ◽  
C2h2 Zinc Finger ◽  
Finger Protein ◽  
C2h2 Zinc Finger Protein

scholarly journals Cys2/His2 zinc-finger protein family of petunia: Evolution and general mechanism of target-sequence recognition

1998 ◽  
Vol 26 (2) ◽  
pp. 608-615 ◽  
Author(s):  
K.-i. Kubo ◽  
A. Sakamoto ◽  
A. Kobayashi ◽  
Z. Rybka ◽  
Y. Kanno ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Protein Family ◽  
General Mechanism ◽  
Target Sequence ◽  
Sequence Recognition ◽  
Finger Protein

Activation of transcriptional activity of HSE by a novel mouse zinc finger protein ZNFD specifically expressed in testis

2012 ◽  
Vol 363 (1-2) ◽  
pp. 409-417 ◽  
Author(s):  
Fengqin Xu ◽  
Weiping Wang ◽  
Chen Lei ◽  
Qingmei Liu ◽  
Hao Qiu ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activity ◽  
Zinc Finger Protein ◽  
Finger Protein

scholarly journals PIAS1 interacts with the KRAB zinc finger protein, ZNF133, via zinc finger motifs and regulates its transcriptional activity

2007 ◽  
Vol 39 (4) ◽  
pp. 450-457 ◽  
Author(s):  
Sang-Jin Lee ◽  
Jae-Rin Lee ◽  
Hwa-Sun Hah ◽  
Young-Hoon Kim ◽  
Jin-Hyun Ahn ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activity ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Zinc Finger Motifs

scholarly journals Characterization and evolutionary origin of novel C2H2 zinc finger protein (ZNF648) required for both erythroid and megakaryocyte differentiation in humans

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Daniel C. J. Ferguson ◽  
Juraidah Haji Mokim ◽  
Marjolein Meinders ◽  
Edmund R. R. Moody ◽  
Tom A. Williams ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Sequence Similarity ◽  
Zinc Finger Domain ◽  
Erythroid Cells ◽  
Coding Region ◽  
Finger Protein ◽  
C Terminus ◽  
N Terminus ◽  
Megakaryocyte Differentiation

Human ZNF648 is a novel poly C-terminal C2H2 zinc finger protein identified amongst the most dysregulated proteins in erythroid cells differentiated from iPSC. Its nuclear localisation and structure indicate it is likely a DNA-binding protein. Using a combination of ZNF648 overexpression in an iPSC line and primary adult erythroid cells, ZNF648 knockdown in primary adult erythroid cells and megakaryocytes, comparative proteomics and transcriptomics we show that ZNF648 is required for both erythroid and megakaryocyte differentiation. Orthologues of ZNF648 were detected across Mammals, Reptilia, Actinopterygii, in some Aves, Amphibia and Coelacanthiformes suggesting the gene originated in the common ancestor of Osteichthyes (Euteleostomi or bony fish). Conservation of the C-terminal zinc finger domain is higher, with some variation in zinc finger number but a core of at least six zinc fingers conserved across all groups, with the N-terminus recognisably similar within but not between major lineages. This suggests the N-terminus of ZNF648 evolves faster than the C-terminus, however this is not due to exon-shuffling as the entire coding region of ZNF648 is within a single exon. As for other such transcription factors, the N-terminus likely carries out regulatory functions, but showed no sequence similarity to any known domains. The greater functional constraint on the zinc finger domain suggests ZNF648 binds at least some similar regions of DNA in the different organisms. However, divergence of the N-terminal region may enable differential expression, allowing adaptation of function in the different organisms.

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