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in this video we continue talking about
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transcription with a particular focus on
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eukariotic
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transcription so transcription as we
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have seen before is the process whereby
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the information in the DNA is converted
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into RNA molecules and when we think
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about it in terms of genes we have a
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piece of DNA where we have a coding
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region the start of the transcription in
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this genene is called the transcription
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start site which is the plus one site
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all things on the right side of the TSS
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are referred to as Downstream and all
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things left side of the TSS are referred
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to be on the Upstream we saw in the
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procaryotic transcription case the
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promoters of the genes were strictly
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present Upstream of the genes but in
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eukariotic genes the promoter can be
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present Downstream of the TSS as well
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and they often also overlap with the
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coding region so in this video we will
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explore exp the promoter structure of
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eukaryotic genes so let's begin by
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defining promoters it is a DNA sequence
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that defines where the transcription of
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a gene begins via the RNA polymerise and
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its Associated factors so let's dive
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into the
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promoters let's begin by drawing a
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cartoon of the DNA where we have the two
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strands running anti- parallel the TSS
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will be the plus one site for the Gene
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and we will have plus two plus3 and so
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on towards the downstream and -1 -2
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positions and so on on the Upstream
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notice that there is no site zero so the
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most common promoter element that we
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hear about in new curiot is the Tata box
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flanking the upstream and the downstream
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location of the Tara box we sometimes
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find Bru and b d elements if we go
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further Upstream we find something known
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as the C cat box and even further we can
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sometimes find a GC box and we will
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discuss these guys in details in a bit
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so these are the promoters which are
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strictly Upstream of the TSS now there
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is a promoter called The initiator Motif
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which overlaps the TSS and therefore
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flanks both the upstream and the
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downstream
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regions and this is the overlapping
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promoter type that I mentioned
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previously often Downstream of initiator
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we can find an Associated promoter
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element called mte and in some other
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cases we can also find DPE and in rare
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cases we also have some specific ones
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known as the
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xcp1 in this video however we won't be
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discussing
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xcp1 okay so let's now discuss these
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guys in a slightly more
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detail let's start with the Tata box
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this is present between -31 to -25 and
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it has a consensus sequence t a t a w a
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a r the W and R are the iopac symbols
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and if you want to learn more about them
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I have some links in the description
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that you can check the sequence binds
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tf2d which is a transcription factor and
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more specifically it is the tbp subunit
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of the tf2d that is involved in The
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Binding the tbp refers to the binding
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protein tf2d or transcription Factor 2D
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is involved in recruiting RNA polymerase
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to the promoter and in the procaryotic
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promoter video we said that the
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procaryotic homologue of tatab box could
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be the -10 element which is also known
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as the pnau Box flanking the tarab box
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we have the BR Elements which stand for
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B recognition elements the B here refers
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to the fact that these elements are
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recognized by tf2b transcription Factor
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the U in the B refers to the Upstream
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location of this element relative to the
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Tata box its consensus is SSR cgc CG so
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it makes this a very GC Rich region the
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Upstream location of BR is between -37
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to -32 the other side of the B is
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Downstream which refers to its
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Downstream location and this is present
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between -26 to -20 the consensus of p d
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is fairly at Rich which is in contrast
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to the GC Rich consensus of BR U
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functionally BR elements are considered
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regulatory in nature as they can both
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positively or negatively impact the
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promoter capacity of adjacent motifs in
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this case especially the Tata box now we
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go on a bit further upstream and we can
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find that there is a CCAP at box and
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this is usually seen between 00 to -60
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location the consensus for this is ggcc
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a a
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TCT this box usually binds non-canonical
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transcription factors like nucleo Factor
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proteins from family A B and C it also
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binds some other class of proteins known
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as the ccat enhancer binding proteins
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cbps for short and for its ability to
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bind these non-canonical transcription
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factors the ccat box is also called an
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enhancer like promoter a bit Upstream of
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ccat box is another promoter element
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known as the GC box and this is present
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between 1110
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to15 position and its consensus as the
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name implies is quite GC rich like The
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ccat Box it also binds non-canonical
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transcription factors such as the sp1
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and migy and for this reason GC box
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similar to ccat box is also known as an
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enhancer like promoter now let's talk
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about the promoters on the other side
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and let's start with the initiator which
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as we said previously overlaps the
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downstream and the Upstream parts of the
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TSS the exact location of initiator
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motif is highly variable but you can
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expect to find it somewhere between -6
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and + 45 the consensus of initiator is
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also highly variable in humans for
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instance it has a consensus yya and Wy y
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if you look at initiator motive
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consensus in other eukaryotic organisms
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for example mouse or flies the consensus
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is very different the initiator motive
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is usually Bound by tf2d just like the T
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box a neat fact about initiator among
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the few that we will talk about later is
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that it was was first discovered in a
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tdt gene in lymphocytes the promoter of
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this Gene does not have Tata box which
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led to speculate the discovery of other
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promoter elements and it led to the
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discovery of initiator
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motif finally we have promoters which
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are Downstream of the TSS and these are
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the motif 10 elements mte and the
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downstream promoter element DPE they
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were originally discovered in dropa but
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since they're discovered they have also
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been found in human genes the mte you
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can find between + 18 to plus 27
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position which is strictly Downstream of
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the TSS and likewise DP which is also
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Downstream of TSS is present somewhere
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between -28 to + 33 and just like the
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initiator element these are also Bound
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by tf2d transcription Factor the
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functional capacity of mte and DP is
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considered to to be cooperative and it
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has been shown that their function AIDS
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in the potential of initiator motif to
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begin
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transcription thus they are largely
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involved in regulatory function and
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specifically it is the spacing and
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distance of mte or DP from the initiator
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which determines how strongly they will
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impact the process of transcription
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initiation with this knowledge of
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promoters we can now think about a
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couple of things the first idea is of
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core promoters or basil promoters this
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refers to a minimal stretch of DNA which
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is sufficient to accurately begin
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transcription when we talk about core
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promoters we think about the ones that
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bind canonical transcription factors and
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these are usually the ones that span
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from -35 to+
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35 this also suggests that not all
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promoter elements that we talk about
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here are required to begin the
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transcription so what is more profound
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to realize I I is that you can have a
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gene which only has the Tata box as its
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promoter and nothing else and you can
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have a gene which only has initiator
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Motif in its promoter side and you can
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also have another Gene where you find
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both Tata boxes and initiator Motif at
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the promoters in other cases you may
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have only the Tata box and the BR
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Downstream element so the point is that
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you can have any combination of these
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promoters in a gene now the more
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interesting bit about promoter is the
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misconception about t boxes which if you
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look at the data in human genes is only
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present in about 15% of the genes and
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the misconception is that the T box
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which is bound by tbp is somehow the
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universal promoter which is not the case
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tbp not only binds Tata box it is also
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involved in The Binding of initiator
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motifs if you look at the statistics
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you'll see that almost 40% of the genes
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in humans have initiator motif in their
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promoters and 30% of these 45% don't
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even have Tata boxes so this idea of tab
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box being Universal promoter is not true
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and this idea of universal promoter
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itself is very incorrect because that
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would make the process of transcription
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initiation very
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inflexible the final thing that I wanted
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to add to this video is the idea of
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types of transcription starts which can
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be either focused or dispersed
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so let's say you have a gene where you
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only have one promoter element you will
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always initiate transcription at a
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single spot and that's called a focused
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transcription start but in genes where
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you have multiple promoters in tandem
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you have different choices to begin the
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transcription and this will result in
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dispersed transcription start all right
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so let's quickly summarize what we have
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learned here we have some promoter
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Elements which are located strictly
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Downstream of of the TSS there are some
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which overlap the TSS and there are some
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promoters which are strictly Upstream of
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the TSS a majority of these from -35 to
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+ 35 are referred to as core promoter
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elements and they bind canonical
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transcription factors like tf2d and tf2b
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the distal promoter elements Beyond Nega
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35 buying the non-canonical
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transcription factors like sp1 migy
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CBP and Korea and finally we said that
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tab box is not a universal promoter but
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I would like you to know that the Tata
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box is perhaps one of the oldest
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promoter elements that we know of
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because you can find it in virtually all
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ukots spanning both plant and animals
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and you can even find it in some archa
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bacteria again this does not imply that
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tarab box is a universal promoter
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element and with that we have covered
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the Crux of eukariotic prom elements
