8 research outputs found
Identification of the targets of the human transcription factor patz1
POZ-AT hook-zinc finger protein 1 (PATZ1) is a ubiquitously expressed N-terminal BTB domain containing transcription factor which has a C2H2 type zinc finger DNA binding domain at its C-terminal. According to the recent findings PATZ1 acts both as a suppressor and an activator in a context dependent manner. Even though regulatory role of Patz1 is associated with various cancers, such as Ewing’s Sarcoma and prostate cancer, the target genes of PATZ1 are not known. As a transcription factor remains controversial due to lack of genomic studies. We identified some of the genes that are bound and regulated by the PATZ1 transcription factor in the HCT116 colon cancer cell line by using techniques such as CRISPR/Cas9 genome editing tool, RNA-seq and CHIPseq data analysis. We showed that PATZ1 binds to the promoters of its target genes and regulates their expression by both activating and suppressing these targets. For the first time in literature, we identified transcriptional targets of PATZ1 in HCT116 human colon cancer cell line
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Dimerization choice and alternative functions of ZBTB transcription factors
Zinc Finger DNA-binding domain-containing proteins are the most populous family among eukaryotic transcription factors. Among these, members of the BTB domain-containing ZBTB sub-family are mostly known for their transcriptional repressive functions. In this Viewpoint article, we explore molecular mechanisms that potentially diversify the function of ZBTB proteins based on their homo and heterodimerization, alternative splicing and post-translational modifications. We describe how the BTB domain is as much a scaffold for the assembly of co-repressors, as a domain that regulates protein stability. We highlight another mechanism that regulates ZBTB protein stability: phosphorylation in the zinc finger domain. We explore the non-transcriptional, structural roles of ZBTB proteins and highlight novel findings that describe the ability of ZBTB proteins to associate with poly adenosine ribose in the nucleus during the DNA damage response. Herein, we discuss the contribution of BTB domain scaffolds to the formation of transcriptional repressive complexes, to chromosome compartmentalization and their non-transcriptional, purely structural functions in the nucleus
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Thymosin beta-4 A/T polymorphism and acute coronary syndrome risk
Aim: Acute coronary syndrome (ACS) describes all the clinical conditions
due to myocardial infarction that is caused by decreased blood flow in the
coronary artery. Thymosin beta-4 (Tβ4) plays a significant role in the recovery
of damaged tissues and promoting the survival of cardiomyocytes in ACS. In this
study, it was aimed to determine the Tβ4 A/T (rs75112573) variation in ACS and
its effects on the disease. Methods: This was a prospective
case-control study. Forty-eight patients with ACS and 45 healthy
controls were recruited for this study. Genetic analysis was performed using
polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP).Results: The AT genotype (p<0.001, X2:12.40,
OR:5.42, 95% CI:2.02-14.53) and the A allele (p<0.001, X2:17.22,
OR:6.66, 95% CI:2.61-16.98) frequency was found significantly higher in the
patient group, while in the control group the TT genotype was statistically
higher (p<0.001, X2:17.22, OR:2.13, 95% CI:1.44-3.16). LDL-cholesterol levels in the patient group
(p<0.001, 95% CI:30.12-55.90), and HDL-cholesterol levels in the control
group (p<0.001, 95% CI:5.30-15.34) were significantly higher. In the patient
group, total cholesterol and HDL-cholesterol levels were found significantly
higher in AT genotype carriers compared to the AA genotype carriers (p=0.036,
95% CI:0.59-17.25), while VLDL-cholesterol levels were higher in the AA
genotype carriers compared to the AT (p=0.011, 95% CI:6.73-49.86), and TT (p=0.018,
95% CI:4.95-49.49) genotype carriers.
Conclusion: It can be concluded that carrying the Tβ4
A/T (rs75112573) gene polymorphism AT genotype and the A allele may increase
risk of ACS
Deneysel Obezite Modeli Oluşturulan C57BL/6J Soyu Farelerde Ghrelin Gen Ekspresyonları ve Protein Düzeylerinin İncelenmesi
Sibling rivalry among the ZBTB transcription factor family: homodimers versus heterodimers
The BTB domain is an oligomerization domain found in over 300 proteins encoded in the human genome. In the family of BTB domain and zinc finger–containing (ZBTB) transcription factors, 49 members share the same protein architecture. The N-terminal BTB domain is structurally conserved among the family members and serves as the dimerization site, whereas the C-terminal zinc finger motifs mediate DNA binding. The available BTB domain structures from this family reveal a natural inclination for homodimerization. In this study, we investigated the potential for heterodimer formation in the cellular environment. We selected five BTB homodimers and four heterodimer structures. We performed cell-based binding assays with fluorescent protein–BTB domain fusions to assess dimer formation. We tested the binding of several BTB pairs, and we were able to confirm the heterodimeric physical interaction between the BTB domains of PATZ1 and PATZ2, previously reported only in an interactome mapping experiment. We also found this pair to be co-expressed in several immune system cell types. Finally, we used the available structures of BTB domain dimers and newly constructed models in extended molecular dynamics simulations (500 ns) to understand the energetic determinants of homo- and heterodimer formation. We conclude that heterodimer formation, although frequently described as less preferred than homodimers, is a possible mechanism to increase the combinatorial specificity of this transcription factor family