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Cell Biology International (2012) 36, 177–182 (Printed in Great Britain)

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Hypothesis article

Retention and transmission of active transcription memory from progenitor to progeny cells via ligand-modulated transcription factors: elucidation of a concept by BIOPIT model

Sanjay Kumar, Mallampati Saradhi, Nagendra K. Chaturvedi and Rakesh K. Tyagi¹

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India

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.

Key words: mitotic chromatin, nuclear foci, nuclear receptor (NR), transcription memory

Abbreviations: AR, androgen receptor, BIOPIT, biomolecular imprints offered to progeny for inheritance of traits, CBP, CREB (cAMP-response-element-binding protein)-binding protein, ChIP, chromatin immunoprecipitation, DHT, dihydrotestosterone, FP, fluorescent protein, GFP, green fluorescent protein, GRIP1, glucocorticoid receptor-interacting protein 1, HMG, high mobility group, HSF2, heat shock transcription factor 2, NF-Y, nuclear factor Y, NR, nuclear receptor, PXR, pregnane X receptor, SRC-1, steroid receptor co-activator 1, TBP, TATA-box binding protein

¹To whom correspondence should be addressed (email rktyagi@yahoo.com or rkt2300@mail.jnu.ac.in).

Received 23 October 2009/10 June 2011; accepted 18 October 2011

Published as Cell Biology International Immediate Publication 18 October 2011, doi:10.1042/CBI20090329

© The Author(s) Journal compilation © 2012 Portland Press Limited