Cys2His2 zinc finger protein family: Classification, functions, and major members

Razin, Sergey V.; Borunova, V. V.; Maksimenko, Oksana; Kantidze, Omar L.

doi:10.1134/s0006297912030017

Cited by 156 publications

(130 citation statements)

References 153 publications

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“…Insm1 contains five zinc finger domains of the C2H2 type, a motif frequently associated with transcription factors (Razin et al, 2012). At the very N-terminus, Insm1 contains a SNAG domain (Grimes et al, 1996), which was first identified in Snail/Slug and Gfi1 and Gfi1b zinc finger transcription factors and recruits Rcor1, the histone deacetylases Hdac1 and Hdac2 and the histone demethylase Kdm1a (Saleque et al, 2007;Lin et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors

et al. 2013

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The Insm1 gene encodes a zinc finger factor expressed in many endocrine organs. We show here that Insm1 is required for differentiation of all endocrine cells in the pituitary. Thus, in Insm1 mutant mice, hormones characteristic of the different pituitary cell types (thyroid-stimulating hormone, follicle-stimulating hormone, melanocyte-stimulating hormone, adrenocorticotrope hormone, growth hormone and prolactin) are absent or produced at markedly reduced levels. This differentiation deficit is accompanied by upregulated expression of components of the Notch signaling pathway, and by prolonged expression of progenitor markers, such as Sox2. Furthermore, skeletal muscle-specific genes are ectopically expressed in endocrine cells, indicating that Insm1 participates in the repression of an inappropriate gene expression program. Because Insm1 is also essential for differentiation of endocrine cells in the pancreas, intestine and adrenal gland, it is emerging as a transcription factor that acts in a pan-endocrine manner. The Insm1 factor contains a SNAG domain at its N-terminus, and we show here that the SNAG domain recruits histone-modifying factors (Kdm1a, Hdac1/2 and Rcor1-3) and other proteins implicated in transcriptional regulation (Hmg20a/b and Gse1). Deletion of sequences encoding the SNAG domain in mice disrupted differentiation of pituitary endocrine cells, and resulted in an upregulated expression of components of the Notch signaling pathway and ectopic expression of skeletal muscle-specific genes. Our work demonstrates that Insm1 acts in the epigenetic and transcriptional network that controls differentiation of endocrine cells in the anterior pituitary gland, and that it requires the SNAG domain to exert this function in vivo.

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Section: Introductionmentioning

confidence: 99%

Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors

et al. 2013

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“…Unlike the animal PRDM9 protein, PbZfp lacks the methyltransferase SET domain and does not have KRI domains typical of the members of the KRAB family of animal C 2 H 2 ZnF proteins. Thus, while not directly related to these animal proteins, PbZfp shows an unusual resemblance to animal C 2 H 2 ZnF proteins in having a multiplicity of C 2 H 2 Zfd (22). Notably, orthologs of PbZfp exhibiting greater sequence divergence are also seen in other Apicomplexa species, such as piroplasms (e.g., Theileria spp.…”

Section: Resultsmentioning

confidence: 97%

“…The C2H2-type Zfd, represented by two cysteine and two histidine residues separated by~12 amino acids acting as ligands to a zinc atom, are widespread in most DNA-binding proteins (21,22). In animals, proteins with multiple C 2 H 2 ZnFs are transcription factors regulating gene expression and acting during cell differentiation and development.…”

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confidence: 99%

Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response

Gopalakrishnan

Aly

Aravind

et al. 2017

mBio

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In sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in Plasmodium led to identification of a gene encoding a protein that contains 11 copies of C 2 H 2 zinc fingers (ZnF). Reverse genetic approaches were used to create Plasmodium berghei parasites either lacking expression of full-length Plasmodium berghei zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc]). Mice infected with KO parasites survived two times longer (P Ͻ 0.0001) than mice infected with wild-type (WT) parasites. In mosquito transmission experiments, the infectivity of KO and Trunc parasites was severely compromised (Ͼ95% oocyst reduction). KO parasites revealed a total lack of trimethylation of histone 3 at several lysine residues (K4, K27, and K36) without any effect on acetylation patterns (H3K9, H3K14, and H4K16). Reduced DNA damage and reduced expression of topoisomerase-like Spo11 in the KO parasites with normal Rad51 expression further suggest a functional role for PbZfp during genetic recombination that involves DNA double-strand break (DSB) formation followed by DNA repair. These finding raise the possibility of some convergent similarities of PbZfp functions to functions of mammalian PRDM9, also a C 2 H 2 ZnF protein with histone 3 lysine 4 (H3K4) methyltransferase activity. These functions include the major role played by the latter in binding recombination hotspots in the genome during meiosis and trimethylation of the associated histones and subsequent chromatin recruitment of topoisomerase-like Spo11 to catalyze DNA DSB formation and DMC1/Rad51-mediated DNA repair and homologous recombination.IMPORTANCE Malaria parasites are haploid throughout their life cycle except for a brief time period when zygotes are produced as a result of fertilization between male and female gametes during transmission through the mosquito vector. The reciprocal recombination events that follow zygote formation ensure orderly segregation of homologous chromosomes during meiosis, creating genetic diversity among offspring. Studies presented in the current manuscript identify a novel C2H2 ZnFcontaining protein exhibiting multifunctional roles in parasite virulence, mosquito transmission, and homologous recombination during meiosis. Understanding the transmission biology of malaria will result in the identification of novel targets for transmission-blocking intervention approaches.

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“…C2H2 zinc-finger proteins (ZFPs) constitute the largest family of transcription factors in higher eukaryotes (16)(17)(18). C2H2-ZFPs were shown to be required for key cell processes, including transcriptional regulation, development, pathogen defense and stress responses.…”

Section: Discussionmentioning

confidence: 99%

Zinc finger protein 667 expression is upregulated by cerebral ischemic preconditioning and protects cells from oxidative stress

et al. 2013

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Abstract. Brain ischemic injury is associated with clinical emergencies such as acute ischemic and hemorrhagic stroke, head trauma, prolonged severe hypotension and cardiac arrest. Ischemic preconditioning (IPC) is the most powerful endogenous mechanism against ischemic injury. However, the majority of IPC treatments are invasive and thus impractical in the clinical setting. Identifying the endogenous neuroprotective mechanism induced by IPC is important for developing new strategies to reduce stroke severity. Zinc finger protein 667 (ZNF667) is a novel zinc finger protein that is upregulated by myocardial IPC. However, its functional role in neuronal ischemia has not been elucidated. In this study, the changes of ZNF667 expression on cerebral IPC and its potential neuroprotective function were investigated. The cerebral ischemia model was established by ameliorated four-vessel occlusion in rats. The northern blot results demonstrated that ZNF667 expression was increased in the hippocampus and cortex at 12 and 24 h after cerebral ischemic pretreatment. To investigate the neuroprotective function of ZNF667, enhanced green fluorescent protein (EGFP)-ZNF667 fusion protein was expressed in C2C12 and brain astrocytoma cells and its subcellular localization was detected by confocal microscopy. EGFP-ZNF667 fusion proteins were localized in the nucleus of C2C12 and brain astrocytoma cells, indicating that ZNF667 may act as a transcription factor in neural cells. To mimic oxidative stress associated with ischemia/reperfusion injury, hydrogen peroxide (H 2 O 2 ) was used to treat cells. Cell viability was measured by the lactate dehydrogenase (LDH) and WST-1 assays. A decrease in viability was detected in C2C12 and astrocytoma cells following H 2 O 2 treatment, whereas ZNF667 gene overexpression significantly improved cell viability following H 2 O 2 treatment. These results suggested that ZNF667 plays a neuroprotective role by acting as a transcription factor in cerebral IPC.

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Cys2His2 zinc finger protein family: Classification, functions, and major members

Cited by 156 publications

References 153 publications

Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors

Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors

Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response

Zinc finger protein 667 expression is upregulated by cerebral ischemic preconditioning and protects cells from oxidative stress

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