Lecture 19 - Non-coding Genome Flashcards
What is the central dogma
Describes how cells read and express the information encoded in their genome
What % of the genome encodes for protein coding genes
2%
What is the ENCODE project
catalogue all functional elements in the human genome
What. does transcriptional regulatory system play a central part in
in controlling many fundamental biological
processes by ensuring the correct expression of specific genes e.g. lineage differentiation
How do cells become different during development
the regulated expression
of thousands of different genes in time
and space causing stem cells to adopt
different fates and differentiate
into more specialised cell types
What diseases arise from a breakdown in the transcription regulatory system
Cancer and human developmental disorders
How many subunits are in RNA pol II
12
How does RNA pol II work in initiation
Recruited to target genes along with General Transcription Factors
(GTFs) and regulatory proteins in a complex called RNA pol II
holoenzyme (INITIATION)
RNA pol II moves stepwise along the DNA unwinding the double helix at its active site
How does RNA pol II work in Elongation
Complementary nucleotides are added in a
sequential manner using the anti-sense DNA
strand as a template (ELONGATION)
How does RNA pol II work in termination
RNA pol II stops at the end of a gene and is
released from the DNA strand
What are the different classes of cis-regulatory DNA sequences to ensure proper transcriptional control of RNA pol II expressed genes
Gene Promoters
Enhancers
Silencers
Insulator elements
(Control at which times (temporal), under what conditions,
and in what tissues (spatial) a gene will be expressed)
What is the TSS
Transcription Start site
Genomic DNA sequences that define the position where transcription
of a gene by RNA pol II begins
Where are gene promoters recruited to
Directly upstream of the target gene
What are DNA sequence motifs bound to in a stepwise manner along w RNA polII
GTFs
What are some examples of GTFs
(TBP, TFIID, TFIIB, TFIIF, TFIIE, and TFIIH)
What do Enhancers and silencers do
DNA sequences located on the same chromosome (cis) as the genes they regulate
Can be located upstream or downstream of their target genes, and within introns and coding regions
Can be located many kilobases away from their target promoters (distal)
Modulate the rate of promoter transcription
What do TFs do
Transcription Factors ‘read’ the sequence of cis regulatory DNA and bind to specific motifs
Where are DNA bound TFs that interact with GTFs and RNA pol II assemble
At the promotor
What do TFs often contact with
with intermediary proteins
called transcriptional coactivators and
corepressors (such as Mediator) that don’t
directly bind DNA
What do enhancer elements do
Enhancer elements speed up the rate of RNA pol II-GTF complex assembly to promote transcription from the gene promoter
How do silencers work
block RNA pol II-GTF complex assembly and slow down transcription
(and/or function to modify chromatin structure)
What do insulator elements do
Class of DNA sequences that function to prevent the inappropriate regulation of adjacent genes
Situated between an enhancer and promotor
How do insulator elements work
Block the action of a distal enhancer on a promoter
Control the gene or set of genes that an enhancer can regulate
Prevent the spread of condensed chromatin sequences
What are barrier elements
Specialised type of insulator sequence
What is an example of correct spatial and temporal gene expression
Msx1 homeodomain transcription factor is an important regulator of pluripotency
Expressed in mesenchymal progenitor cells in the developing embryo (differentiate into a variety of cell types, including: osteoblasts, chondrocytes, myocytes and adipocytes)
What does FANTOM stand for
Functional and Taxonomic analysis of metagenomes
What does ENCODE stand for
ENCyclopaedia Of DNA Elements project
What % of the genome contains open chromatin
15.2%
What % of the genome is bound by a transcription factor
8.1%
How many regions have promotor-like features ((1) broad, CG rich, TATA-less promoters
(2) narrow (single TSS), TATA-box-containing promoters)
70,292
How many putative cis-regulatory DNA sequences
399,124
What are ncRNAs
non-coding RNAs
What are the 2 classes of ncRNAs
Housekeeping ncRNAs
Regulatory ncRNAs
what are the types of regulatory ncRNAs
Short (<200 nucleotides)
Micro RNAs (miRNA)
Small interfering RNAs (siRNA)
Piwi interacting RNAs (piRNA)
Long non-coding (>200 nucleotides)
lncRNAs
What are some features of lncRNAs
long non-coding RNAs
RNA polymerase II transcribed regulatory ncRNAs
Greater than 200 nt in length
Do not encode for protein
Possess a polyA tail and 5’ 7-methylguanosine cap
Fewer exons and shorter transcript length compared to mRNAs
More tissue restricted expression than mRNAs
Located in either the nucleus or the cytoplasm
