Molecular Biology

1. Transcriptional Regulatory Elements

2. The completion of the human genome sequence led to the
cataloging of∼20,000–25,000 protein-coding genes
To understand the molecular mechanisms that govern
specific expression patterns it is important to identify the
transcriptional regulatory elements

3. Transcriptional regulation
One of the mechanisms through which protein levels in the
cell are controlled is through transcriptional regulation.
Certain regions, called cis-regulatory elements, on the
DNA are footprints for the transacting proteins involved in
transcription, either for the positioning of the basic
transcriptional machinery or for the regulation

4. Transcriptional regulatory elements
 Activator
 promoter:
 Core Promoter
 Proximal Promoter Elements
 distal regulatory elements:
 Enhancers
 Silencers
 Insulators

5. Activators
In general, activators are sequence-specific DNA-binding
proteins whose recognition sites are usually present in
sequences upstream of the core promoter
Examples of activator families:
 Cysteine rich zinc finger
 helix-loop-helix (HLH)
 basic leucine zipper (bZIP)
 DNA binding domain
The activity of an activator may be modulated by coactivators

6. Activators

7. Cis-acting transcriptional regulatory
elements
Genes transcribed by RNA polymerase II typically contain two
distinct families of cis-acting transcriptional regulatory elements:
 promoter
 distal regulatory element
These cis-acting transcriptional regulatory elements contain
recognition sites For trans-acting DNA-binding transcription
factors, which function either to enhance or repress transcription

8. Transcriptional regulatory
elements

9. Transcriptional regulatory
elements

10. Promoter
promoter is a region of DNA that initiates transcription of
a particular gene
Promoters are located near the transcription start sites of
genes.
Promoters can be about 100–1000 base pairs long.

11. Core Promoter

12. PIC :
Binding of
regulatory proteins is
required formation of
the PIC
(pre-initiation
complex).

13. Enhancers
Enhancer is a short (50-1500 bp) region of DNA that can
be bound with proteins (activators) to activate transcription
of a gene or genes.
These proteins are usually referred to as transcription factors

14. Enhancers

15. Silencers
Silencer is a DNA sequence capable of binding
transcription regulation factors, called repressors.
Silencers are sequence-specific elements that confer a
negative effect on the transcription of a target gene
Typically, they function independently of orientation and
distance from the promoter, although some position-
dependent silencers have been encountered.

16. Insulators
Insulators function to block genes from being affected by
the transcriptional activity of neighboring genes.
They can block such interactions such as block enhancer-
promoter
It is thought that an insulator must reside between the
enhancer and promoter to inhibit their subsequent
interactions.