Retention and transmission of active transcription memory from progenitor to progeny cells via ligand-modulated transcription factors: elucidation of a concept by BIOPIT model.
Observations made in live cells have clearly demonstrated that agonist-activated steroid/nuclear receptors reorganize in the nucleoplasm into hundreds of discrete speckled structures commonly referred to as nuclear foci. Subsequent studies have shown that nuclear foci are formed only with agonist- and not with pure antagonist-bound receptors. Also, the other accessory components of transcriptional machinery co-localize in nuclear foci with the activated receptors, suggesting these to be active gene transcription sites. Recently, it has been observed that during mitosis nuclear foci present in interphase of progenitor cells co-migrate with condensing chromatin and are inherited into the progeny cells. Ensuing events imply that as memory, the cells inherit only a biomolecular blueprint of transcription status over to next generations to express and sustain their characteristic proteome. Thus, cells achieve self-renewal via mitosis but not without ensuring that the characteristic proteome and traits are distinctively preserved during this transcription phase. This mechanism, although somewhat analogous to epigenetic marking, differs in Nature since transcription factors themselves execute this transmission. To uphold the mechanistic distinctions the phenomenon has been termed BIOPIT (biomolecular imprints offered to progeny for inheritance of traits). The BIOPIT model proposed herein attempts to explain how the disruption of BIOPIT markings by therapeutic anti-hormones or endocrine disruptors over prolonged periods may lead to eradication of cellular transcription memory with deleterious cellular consequences. It is anticipated that our model has the potential to explain the concerted actions and consequences of ligand-receptor interactions with the chromatin in the perspective of normal and aberrant physiological situations.
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
Sanjay
S
Kumar
Mallampati
M
Saradhi
Nagendra K
NK
Chaturvedi
Rakesh K
RK
Tyagi
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism; D006801:Humans; D007399:Interphase; D008024:Ligands; D008938:Mitosis; D008954:Models, Biological; D020543:Proteome / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D008024:Ligands; D020543:Proteome; D014157:Transcription Factors