**Acknowledgements**

histone ubiquitination and prevents its nuclear translocation and ubiquitin ligase activity [163]. Human PIWIL4 function is crucial in accurate spermatogenesis, and genetic polymorphisms of PIWIL4 gene are significantly correlated with defective spermatogenesis associated

In *Drosophila*, PIWI proteins induce ovary tissue morphogenesis through c-Fos inactivation at posttranscriptional level [165]. They are implicated in development of eye color [144]. In silkworm, fempiRNA, a piRNA located on female W-chromosome, is pivotal in sex determination by repressing masculinization mRNA at posttranscriptional level [167]. At early stages of human embryonic lungs development, PIWIL1, PIWIL2, and PIWIL4 levels of expression are strongly upregulated from 6th week to 9th week and then decline [168]. In human, PIWIL1 and PIWIL2 have crucial role in neural polarization and radial migration during maturation

The PIWI-piRNA pathway has pivotal role in numerous physiological processes.

PIWI proteins and piRNAs are instrumental in synaptic plasticity and stabilization of longterm memory through serotonin-dependent suppression of CREB2 at transcription level that is induced by methylation of CpG islands in the promoter region of the *CREB2* gene [59]. In rodents, several piRNAs are upregulated in hippocampal neurons and Miwi associated with piRNAs control dentritic spine development and morphogenesis [149]. Mili expression is associated with anxiety and locomotory drive [54]. In humans, PIWIL1 controls cortical neuron activity through modulation of microtubule-associated proteins (MAPs) expression [169]. Furthermore, mutations of PIWIL2 and PIWIL4 are significantly correlated with autism [170].

PIWI proteins and piRNAs have crucial role in self-renewal, regeneration, and homeostasis. In planarian *Schmidtea mediterranea*, SMEDWI-2 and SMEDWI-3 increase division of adult stem cells to induce regeneration in injured tissues [113]. In jellyfish, Cniwi is upregulated during transdifferentiation of striated muscle into smooth muscle [171]. In humans, PIWI proteins promote hepatocyte regeneration [61] and maintain integrity of

The PIWI-piRNA pathway controls fat metabolism through repression of TEs, and fat metabolism inactivation is associated with depletion of lipid synthesis and storage [60]. PIWIL2 and PIWIL4 modulate pancreatic β-cells function and insulin secretion. Alterations of their levels

of expression were observed in diabetic conditions [55].

with spermatogenesis defect and male infertility [164].

of the cerebral cortex region of the brain [59].

*3.4.7.3. Organogenesis*

248 Chromatin and Epigenetics

*3.4.8. Physiological processes*

*3.4.8.1. Brain plasticity*

*3.4.8.2. Regeneration*

retinal cells [130].

*3.4.8.3. Metabolism*

This work was supported by grant INCa-DGOS-4654.
