Основы биологии_Лекция-11 (2013)

Влияние регуляторных факторов на промотор

•Enhancers, silencers

•5’ region, distal

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•Как белки узнают последовательность ДНК? Мотив «цинковый палец»

–Common motif in DNA binding, e.g. SP1 has

(A) The structure of a fragment of a mouse gene regulatory protein bound to a specific DNA site. This protein recognizes DNA using three zinc fingers of the Cys-Cys-His-His type arranged as direct repeats. (B) The three fingers have similar amino acid sequences and contact the DNA in similar ways. In both (A) and (B) the zinc atom in each finger is represented by a small sphere. (Adapted from N. Pavletich and C. Pabo, Science252:810-817, 1991. © 1991 the AAAS.)

• Мотив «спираль-поворот-спираль»

All of the proteins bind DNA as dimers in which the two copies of the recognition helix (red cylinder) are separated by exactly one turn of the DNA helix (3.4 nm). The second helix of the helix-turn-helix motif is colored blue. The lambda repressor and cro proteins control bacteriophage lambda gene expression, and the tryptophan repressor and the catabolite activator protein (CAP) control the expression of sets of E. coli genes.

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•Гомеодомены

–Related to helix-turn-helix bacterial repressors

–Homeobox = 60 AA residues

–E.g. en, eve, Hox, Oct-1, Oct-2 (Oct also have Pou domain next to homeodomain)

The homeodomain is folded into three alfa helices, which are packed tightly together by hydrophobic interactions (A). The part containing helix 2 and 3 closely resembles the helix-turn-helix motif, with the recognition helix (red) making important contacts with the major groove

(B). The Asn of helix 3, for example, contacts an adenine. Nucleotide pairs are also contacted in the minor groove by a flexible arm attached to helix 1. The homeodomain shown here is from a yeast gene regulatory protein, but it is nearly identical to two homeodomains from Drosophila, which interact with DNA in a similar fashion. (Adapted from C. Wolberger et al., Cell 67:517-528, 1991. © Cell Press.)

•Мотив «спираль-петля-спираль» Helix- loop-helix (HLH)

–DNA binding (helix) & dimerization

–Class A: ubiquitouslyh expressed proteins, e.g. E12/E47

–Class B: tissue-specific expression, e.g. MyoD, myogenin, Myf-5

–Myc proteins (separate class)

•Мотив «лейциновая молния

fig 21.15

–Dimerization motif

–E.g. Jun+Fos = AP1

–Gcn4 ->

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Составные части генома человека

•Геном человека состоит из 3,2 миллиардов пар нуклеотидов

•Около 3% генома кодирует белки

•Около 40-50% являются остатками некогда попавших в геном вирусов

•Какова же функция оставшихся 50%?

Варианты последовательностей

•Высокоповторяющиеся

последовательности

–R (repetition frequency) >100,000

–Almost no information, low complexity

•Умеренные повторы

–10<R<10,000

–Little information, moderate complexity

•Уникальные последвоательности

–R=1 or 2

–Much information, high complexity

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Области сателлитных повторов

Human chromosomes, ideograms G-bands

Tandem repeats on every chromosome: Telomeres Centromeres

5 clusters of repeated rRNA genes:

Short arms of chromosomes 13, 14, 15, 21, 22

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