BIOC1306 Enhancers LCR Insulators

what are TADs (topologically associating domains)

chromosomes are arranged into them

interactions increased within, plus decreased outside

CTCF binds inbetwee them

what does CTCF bind

inbetween TADs at insulator elements

what function is CTCF req for

the exhancer blocking function of insulators

what does CFTR form complexes with

cohesin

role of cohesin

holds sister chromatids together following replication until mitosis

mediates loop extrusion until reach a barrier on chromosome e.g. CTCF

binds CTCF at insulator elements, this process forms chromosome loops

which can have loop extrusions too (sub domains)

are all LCRs enhancers

No some can be

others can stop spread of heterochromatin

some only function in wider contect of genome (organise/regulate active chromatin hubs)

is HS1 and HS4 of the beta chicken locus (insulators) both enhancer and chromatin blocking

HS4 is both enhancer blocking and HC barrier

HS1 is enhancer blocking only

3 ways insulators block enhancers

act as decoy promoters

bound by proteins, barrier to pol II tracking

organise chromosome into topologically constrained loops where enhancer interaction with a promoter is blocked

what do many insulating binding factors also bind

bind CTCF, some of them req this binding for their blocking activity

role of USF1 and USF2

bind insulator elements

are responsible for blocking spread of HC function of insulators

they recruit HATs that form H3K9ac mark, prev HP1/Suv39h making H3K9me3 which is repressive (bind HP1)

what is the new model of transcription factories

relaxed model

transcription zones

RNA pol II not fixed there, are not preformed, but are hubs of active gene expression

Genes loop into these areas for transcription

pros and cons of transcription factories

conc transc and slice machinery for efficient initiation of these processes

but possible trans-splicing and chromosome translocations