Epigenetika

Epigenetika — DNK ketma-ketligini oʻzgartirmagan holda genlar ekspressiyasida yuz beradigan oʻzgarishlarni oʻrganuvchi soha^[1]. Epigenetika soʻzidagi grekcha epi- (ἐπι- „ustida, tashqarisida, atrofida“) qoʻshimchasi anʼanaviy DNK ketma-ketligiga asoslangan irsiyat mexanizmidan „tashqari“ yoki unga „qoʻshimcha“ boʻlgan xususiyatlarni anglatadi^[2]. Epigenetika, odatda, hujayra boʻlinishi jarayonida saqlanib qoladigan va genlar ekspressiyasining boshqarilishiga taʼsir koʻrsatadigan oʻzgarishlarni oʻz ichiga oladi^[3]. Hujayraviy va fiziologik belgilardagi bunday taʼsirlar atrof-muhit omillari natijasida yuzaga kelishi yoki normal rivojlanishning bir qismi boʻlishi mumkin.

Ushbu termin, shuningdek, mazkur oʻzgarishlar ortida turgan mexanizmga, yaʼni nukleotidlar ketma-ketligida mutatsiyalar sodir etmasdan, genomda yuz beradigan funksional oʻzgarishlarga ham tegishlidir. Bunday oʻzgarishlarni keltirib chiqaruvchi mexanizmlarga DNK metillanishi va giston modifikatsiyasi misol boʻla oladi. Ularning har biri asosiy DNK ketma-ketligini oʻzgartirmasdan, genlarning namoyon boʻlish tartibini oʻzgartiradi^[4]. Bundan tashqari, kodlamaydigan RNK ketma-ketliklari ham genlar ekspressiyasini boshqarishda asosiy rol oʻynashi isbotlangan^[5]. Genlar ekspressiyasi DNKning susaytiruvchi (saylenser) hududlariga birikuvchi repressor oqsillar yordamida nazorat qilinishi mumkin. Bunday epigenetik oʻzgarishlar hujayraning butun hayoti davomida boʻlinishlar orqali saqlanib qolishi, shuningdek, organizmning DNK ketma-ketligida oʻzgarishlar boʻlmasa-da, bir necha avlod davomida davom etishi mumkin^[6]. Buning oʻrniga, nogenetik omillar organizm genlarining „oʻzini turlicha tutishi“ga (yoki namoyon boʻlishiga) sabab boʻladi^[7].

Evkaliotlar biologiyasida epigenetik oʻzgarishlarga yorqin misol sifatida hujayralar differensiatsiyasi jarayonini koʻrsatish mumkin. Morfogenez davomida totipotent oʻzak hujayralari embrionning turli xil pluripotent hujayra liniyalariga aylanadi, ular esa oʻz navbatida toʻliq ixtisoslashgan hujayralarga aylanadi. Boshqacha aytganda, yagona urugʻlangan tuxum hujayra — zigota — boʻlinishda davom etar ekan, hosil boʻlgan qiz hujayralar ayrim genlarni faollashtirish va boshqalarining ekspressiyasini tormozlash orqali organizmdagi turli hujayra turlariga, jumladan, neyronlar, mushak hujayralari, epiteliylar, qon tomirlarining endoteliylari va boshqalarga aylanadi^[8].

Taʼriflar

Epigenez atamasi XVII asrdan beri ingliz tilida „qoʻshimcha oʻsish“ degan umumiy maʼnoda qoʻllanilib kelmoqda^[9]. Ilmiy nashrlarda epigenetika termini 1930-yillardan boshlab koʻrina boshlagan boʻlsa-da, uning zamonaviy maʼnosi faqat 1990-yillarga kelib shakllandi^[10].

2008-yilda Cold Spring Harbor konferensiyasida epigenetik belgi tushunchasiga quyidagicha taʼrif berildi^[11]: „DNK ketma-ketligini oʻzgartirmasdan, xromosomadagi oʻzgarishlar natijasida yuzaga keladigan barqaror irsiy fenotip“. Shunga qaramay, irsiy boʻlmagan belgilarni ham oʻz ichiga oluvchi muqobil taʼriflar hali ham keng qoʻllanilmoqda^[12].

Waddington kanalizatsiyasi, 1940-yillar

Xromosomalar ekspressiyasiga taʼsir qiluvchi epigenetik oʻzgarishlar haqidagi gipoteza rus biologi Nikolay Kolsov tomonidan ilgari surilgan edi^[13]. Britaniyalik embriolog C. H. Waddington 1942-yilda „epigenez“ tushunchasiga tayanib, Valentin Haeckerning „fenogenetika“ (Phänogenetik) terminiga parallel ravishda „epigenetika“ terminini fanga kiritdi^[14]. Oʻsha davr biologiyasi kontekstida epigenez embrional rivojlanish jarayonida hujayralarning dastlabki totipotent holatidan differensiatsiya boʻlishini anglatardi^[15].

Waddington bu terminni kiritgan paytda genlarning fizik tabiati va ularning irsiyatdagi roli hali maʼlum emas edi. U bu tushunchadan genetik komponentlarning fenotipni shakllantirishda atrof-muhit bilan qanday oʻzaro taʼsir qilishi haqidagi konseptual model sifatida foydalangan. U biologik rivojlanish uchun metafora sifatida „epigenetik landshaft“ iborasini qoʻlladi. Waddingtonning fikricha, hujayra taqdiri rivojlanish jarayonida u „kanalizatsiya“ deb atagan jarayon orqali belgilanadi. Bu xuddi marmar sharchasining eng past nuqtaga qarab dumalab tushishiga oʻxshaydi^[16]. Waddington hujayra turi differensiatsiyasining ortga qaytmas darajada kuchayib borishini sharchalar (hujayralar analogi) harakatlanadigan vodiylar orasida koʻtarilib turgan qirralar sifatida tasvirlashni taklif qildi^[17].

Soʻnggi vaqtlarda Waddingtonning epigenetik landshaft haqidagi tushunchasi hujayra taqdirini oʻrganishda tizimli dinamika yondashuvi kontekstida qatʼiy shakllantirildi^[18]^[19]. Hujayra taqdirini aniqlash muayyan dinamikalarni, masalan, attraktor-konvergensiya (attraktor muvozanat nuqtasi, chekli sikl yoki noodatiy attraktor boʻlishi mumkin) yoki ossilyator dinamikani namoyon qilishi bashorat qilinmoqda^[19].

Yana qarang

Manbalar

↑ "Epigenetics: definition, mechanisms and clinical perspective". Seminars in Reproductive Medicine 27 (5): 351–7. September 2009. doi:10.1055/s-0029-1237423. PMID 19711245. PMC 2791696. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2791696. "In the original sense of this definition, epigenetics referred to all molecular pathways modulating the expression of a genotype into a particular phenotype. Over the following years, with the rapid growth of genetics, the meaning of the word has gradually narrowed. Epigenetics has been defined and today is generally accepted as 'the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence.'"
↑ „Beware the pseudo gene genies“. The Guardian (2015-yil 19-iyul).
↑ "What do you mean, "epigenetic"?". Genetics 199 (4): 887–896. April 2015. doi:10.1534/genetics.114.173492. PMID 25855649. PMC 4391566. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4391566.
↑ "Epigenetic modifications in cancer". Clinical Genetics 81 (4): 303–311. April 2012. doi:10.1111/j.1399-0004.2011.01809.x. PMID 22082348. PMC 3590802. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3590802.
↑ "The Importance of ncRNAs as Epigenetic Mechanisms in Phenotypic Variation and Organic Evolution". Frontiers in Microbiology 8. 2017. doi:10.3389/fmicb.2017.02483. PMID 29312192. PMC 5744636. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5744636.
↑ "Perceptions of epigenetics". Nature 447 (7143): 396–398. May 2007. doi:10.1038/nature05913. PMID 17522671. https://archive.org/details/sim_nature-uk_2007-05-24_447_7143/page/396.
↑ „What genes remember“ (2008-yil 1-may). 2008-yil 1-mayda asl nusxadan arxivlangan. Qaraldi: 2012-yil 26-iyul.
↑ "Stability and flexibility of epigenetic gene regulation in mammalian development". Nature 447 (7143): 425–32. May 2007. doi:10.1038/nature05918. PMID 17522676. https://archive.org/details/sim_nature-uk_2007-05-24_447_7143/page/424.
↑ Oxford English Dictionary: "The word is used by W. Harvey, Exercitationes 1651, p. 148, and in the English Anatomical Exercitations 1653, p. 272. It is explained to mean 'partium super-exorientium additamentum', 'the additament of parts budding one out of another'."
↑ The Developing Genome: An Introduction to Behavioral Epigenetics. Oxford University Press, 2015. ISBN 978-0-19-992235-2. Andoza:Pn
↑ "An operational definition of epigenetics". Genes & Development 23 (7): 781–3. April 2009. doi:10.1101/gad.1787609. PMID 19339683. PMC 3959995. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3959995.
↑ „Overview“. NIH Roadmap Epigenomics Project. 2019-yil 21-noyabrda asl nusxadan arxivlangan. Qaraldi: 2013-yil 7-dekabr.
↑ Morange M. La tentative de Nikolai Koltzoff (Koltsov) de lier génétique, embryologie et chimie physique, J. Biosciences. 2011. V. 36. P. 211-214
↑ "The epigenotype". Endeavour 1: 18–20. 1942. https://archive.org/details/sim_endeavour_1942-01_1_1/page/18. „For the purpose of a study of inheritance, the relation between phenotypes and genotypes […] is, from a wider biological point of view, of crucial importance, since it is the kernel of the whole problem of development.“
↑ See preformationism for historical background. Oxford English Dictionary: „the theory that the germ is brought into existence (by successive accretions), and not merely developed, in the process of reproduction. […] The opposite theory was formerly known as the 'theory of evolutionʼ; to avoid the ambiguity of this name, it is now spoken of chiefly as the 'theory of preformationʼ, sometimes as that of 'encasementʼ or 'emboîtementʼ.“
↑ The Epigenetics of Birds. Cambridge University Press, 2014. ISBN 978-1-107-44047-0. Andoza:Page needed
↑ "In search of evolutionary developmental mechanisms: the 30-year gap between 1944 and 1974". Journal of Experimental Zoology Part B: Molecular and Developmental Evolution 302 (1): 5–18. January 2004. doi:10.1002/jez.b.20002. PMID 14760651.
↑ "Floral morphogenesis: stochastic explorations of a gene network epigenetic landscape". PLOS ONE 3 (11). 3 November 2008. doi:10.1371/journal.pone.0003626. PMID 18978941. PMC 2572848. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2572848.
1 2 "Branching and oscillations in the epigenetic landscape of cell-fate determination". Progress in Biophysics and Molecular Biology 117 (2–3): 240–249. March 2015. doi:10.1016/j.pbiomolbio.2015.01.006. PMID 25641423.

Qoʻshimcha oʻqish uchun

"Not really identical: epigenetic differences in monozygotic twins and implications for twin studies in psychiatry". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics 151C (2): 136–41. May 2009. doi:10.1002/ajmg.c.30206. PMID 19378334.
„What is Epigenetics?“. Centers for Disease Control and Prevention (2022-yil 15-avgust). Qaraldi: 2023-yil 11-sentyabr.

Havolalar

„Epigenetics & Inheritance“. learn.genetics.utah.edu. Qaraldi: 2019-yil 17-aprel.
The Human Epigenome Project (HEP)
The Epigenome Network of Excellence (NoE)
Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC)
The Epigenome Network of Excellence (NoE) – public international site
"DNA Is Not Destiny" – Discover magazine cover story
"The Ghost In Your Genes", Horizon (2005), BBC
Epigenetics article at Hopkins Medicine
Towards a global map of epigenetic variation

[Epigenetics_2009_review-1] "Epigenetics: definition, mechanisms and clinical perspective". Seminars in Reproductive Medicine 27 (5): 351–7. September 2009. doi:10.1055/s-0029-1237423. PMID 19711245. PMC 2791696. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2791696. "In the original sense of this definition, epigenetics referred to all molecular pathways modulating the expression of a genotype into a particular phenotype. Over the following years, with the rapid growth of genetics, the meaning of the word has gradually narrowed. Epigenetics has been defined and today is generally accepted as 'the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence.'"

[science-2] „Beware the pseudo gene genies“. The Guardian (2015-yil 19-iyul).

[3] "What do you mean, "epigenetic"?". Genetics 199 (4): 887–896. April 2015. doi:10.1534/genetics.114.173492. PMID 25855649. PMC 4391566. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4391566.

[4] "Epigenetic modifications in cancer". Clinical Genetics 81 (4): 303–311. April 2012. doi:10.1111/j.1399-0004.2011.01809.x. PMID 22082348. PMC 3590802. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3590802.

[5] "The Importance of ncRNAs as Epigenetic Mechanisms in Phenotypic Variation and Organic Evolution". Frontiers in Microbiology 8. 2017. doi:10.3389/fmicb.2017.02483. PMID 29312192. PMC 5744636. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5744636.

[pmid17522671-6] "Perceptions of epigenetics". Nature 447 (7143): 396–398. May 2007. doi:10.1038/nature05913. PMID 17522671. https://archive.org/details/sim_nature-uk_2007-05-24_447_7143/page/396.

[7] „What genes remember“ (2008-yil 1-may). 2008-yil 1-mayda asl nusxadan arxivlangan. Qaraldi: 2012-yil 26-iyul.

[pmid17522676-8] "Stability and flexibility of epigenetic gene regulation in mammalian development". Nature 447 (7143): 425–32. May 2007. doi:10.1038/nature05918. PMID 17522676. https://archive.org/details/sim_nature-uk_2007-05-24_447_7143/page/424.

[9] Oxford English Dictionary: "The word is used by W. Harvey, Exercitationes 1651, p. 148, and in the English Anatomical Exercitations 1653, p. 272. It is explained to mean 'partium super-exorientium additamentum', 'the additament of parts budding one out of another'."

[Moore_2015-10] The Developing Genome: An Introduction to Behavioral Epigenetics. Oxford University Press, 2015. ISBN 978-0-19-992235-2. Andoza:Pn

[pmid19339683-11] "An operational definition of epigenetics". Genes & Development 23 (7): 781–3. April 2009. doi:10.1101/gad.1787609. PMID 19339683. PMC 3959995. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3959995.

[NIH-12] „Overview“. NIH Roadmap Epigenomics Project. 2019-yil 21-noyabrda asl nusxadan arxivlangan. Qaraldi: 2013-yil 7-dekabr.

[13] Morange M. La tentative de Nikolai Koltzoff (Koltsov) de lier génétique, embryologie et chimie physique, J. Biosciences. 2011. V. 36. P. 211-214

[waddington-14] "The epigenotype". Endeavour 1: 18–20. 1942. https://archive.org/details/sim_endeavour_1942-01_1_1/page/18. „For the purpose of a study of inheritance, the relation between phenotypes and genotypes […] is, from a wider biological point of view, of crucial importance, since it is the kernel of the whole problem of development.“

[15] See preformationism for historical background. Oxford English Dictionary: „the theory that the germ is brought into existence (by successive accretions), and not merely developed, in the process of reproduction. […] The opposite theory was formerly known as the 'theory of evolutionʼ; to avoid the ambiguity of this name, it is now spoken of chiefly as the 'theory of preformationʼ, sometimes as that of 'encasementʼ or 'emboîtementʼ.“

[Waddington2014-16] The Epigenetics of Birds. Cambridge University Press, 2014. ISBN 978-1-107-44047-0. Andoza:Page needed

[17] "In search of evolutionary developmental mechanisms: the 30-year gap between 1944 and 1974". Journal of Experimental Zoology Part B: Molecular and Developmental Evolution 302 (1): 5–18. January 2004. doi:10.1002/jez.b.20002. PMID 14760651.

[18] "Floral morphogenesis: stochastic explorations of a gene network epigenetic landscape". PLOS ONE 3 (11). 3 November 2008. doi:10.1371/journal.pone.0003626. PMID 18978941. PMC 2572848. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2572848.

[sciencedirect.com-19] 1 2 "Branching and oscillations in the epigenetic landscape of cell-fate determination". Progress in Biophysics and Molecular Biology 117 (2–3): 240–249. March 2015. doi:10.1016/j.pbiomolbio.2015.01.006. PMID 25641423.

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