Transcript Transcription Regulation (Prof. Fridoon)

Introduction to Molecular Cell
Biology
Transcription Regulation
Dr. Fridoon Jawad Ahmad
HEC Foreign Professor
King Edward Medical University
Visiting Professor LUMS-SSE
Gene Regulation
• Some of genes are expressed in all cells all the time.
Housekeeping genes are responsible for the routine
metabolic functions (e.g. respiration).
• Some are expressed as a cell enters a particular
pathway of differentiation.
• Some are expressed all the time in only those cells
that have differentiated in a particular way.
• Some are expressed only as conditions around and
in the cell change. For example, the arrival of a
hormone may turn on/off certain genes in that cell.
Gene Regulation
Transcription
Regulation
in E. Coli
Inducible & Constitutive Enzymes
Transcription Regulation
in E. Coli
Transcription
Regulation
E. Coli
The Eukaryotic Dilemma
For a cell to develop and function properly it must
turn on the right genes and right time.
Genes are located in the nucleus in a tangled
chromatin material wrapped around histones.
The structure of chromatin
dictates whether a gene can
be transcribed not.
Eu & Hetero Chromatin
DNA Organization
Most of DNA is highly ordered and tightly coiled
around positively charged histone proteins and is
virtually inaccessible to RNA polymerase.
Reorganization
In response to specific
signal a cell may
produce or activate a
transcription activator.
Transcription activator
recognizes and binds a
specific sequence of a
specific gene and work
in conjunction with other
proteins that can alter
chromatin structure.
Reorganization
The alteration may occur by addition of acetyl
groups to histones which reduce positive charge.
Chromatin
remodeling
complex can also
alter the structure
of chromatin to
make it accessible
to transcription
factors that attract
RNA Pol.
Reorganization
RNA Pol then with help of remodeling complex can
move along the gene and make an RNA.
Detailed View
Transcribed region has coding information for
making proteins and is in copied into RNA.
Promoter is upstream of TR and is the core
regulatory region where RNA Pol binds.
Upstream of promoter
are PPE where specific
transcription regulatory
factors activators or
repressors bind here.
Detailed View
Activators can recruit the CRC.
Many genes also have enhancer (1000 nucleotide
away) where specific activators only made by
certain cells can bind.
Detailed View
Activators recruit TFIID to the promoter.
TBP a protein with in TFIID bind TATA sequence
(called TATA box) of DNA.
Most eukaryote
promoters have
TATA box,
which is
located 25bp
upstream of
start site.
Detailed View
TFIID and other factors are required to bind DNA
before RNA Pol can recruited.
The core transcription complex then initiates
transcription.
Transcribing
Multiple Genes
The simultaneous
regulation of widely
separated genes is
possible through
common sequences in
their promoters, to
which the same
regulatory proteins
bind.
RNA Processing
pre-mRNA (freshly transcribed) is processed to
make it functional.
1-Introns are removed during RNA maturation
Mature mRNA
The Evidence
The Mechanism
Intron-exon bounderies have
consensus sequences were
snRNPs bind
RNA of U1 has complementary
bases that bind CS at 5’ exonintron boundery.
RNA of U2 has complementary
bases that bind CS near 3’ intronexon boundery.
RNA Processing
2) The transcribed pre-mRNA is altered by the
addition of a G cap (modified GTP) at the 5′ end to
protect RNA and facilitate translation.
3) After the last codon a poly A tail (100-300) is
added at the 3′ end for export and protection